Search

Background: Isavuconazole (ISA) has a favorable side effect profile that makes it attractive for treatment of invasive fungal infections (IFI). It carries FDA approval for invasive aspergillosis and mucormycosis, but there are fewer data for other organisms and non-pulmonary infections. We conducted this review to investigate how ISA performed at treating IFI, with an especial interest in these non-approved indications., Methods: We retrospectively identified and reviewed 131 patients who received ISA as treatment for IFI at our institution, some of whom received ISA as their first anti-fungal therapy and others who received ISA as either step-down therapy or salvage therapy. We identified the microbiologic cause of infection as well as the anatomic site involved for each patient. We then classified patients according to their response to ISA: namely cured, partially responded, or stabilized., Results: The majority of patients were immunocompromised ( n = 76, 58%). ISA was used primarily as a secondary therapy ( n = 116, 89%); either as a step-down/switching from other agents, or as salvage therapy. The most common reasons for switching to ISA were toxicities with prior agents followed by QT prolongation. Although pulmonary aspergillosis and mucormycosis were represented in more than half of the cohort, ISA was also used off-label for treatment of other organisms such as endemic fungi ( n = 19, 15%) as well as central nervous system (CNS) infections ( n = 15, 11%). We have described the detailed clinical characteristics of these CNS infections cases. The overall clinical response rate varied by type of infection and site involved (57-73% response rate)., Conclusions: We demonstrated encouraging clinical responses, particularly outside the FDA-approved indications, as well as good tolerability. This report highlights the critical need for expanded scope of prospective studies to delineate the efficacy of this better-tolerated agent, especially in central nervous system infections.

Background: Remdesivir is FDA-approved for the treatment of hospitalized patients with severe COVID-19. Many patients improve clinically to allow for hospital dismissal before completing the 5-day course. In a prior work, patients who continued remdesivir in an outpatient setting experienced better 28-day clinical outcomes. Here, we assessed patients' perspectives and the economic impact of this outpatient practice., Methods: Hospitalized patients who received remdesivir for COVID-19 at Mayo Clinic, Rochester, from 11/6/2020 to 11/5/2021 and were dismissed to continue remdesivir in the outpatient setting were surveyed. The cost of care was compared between those who remained hospitalized versus those who were dismissed., Results: 93 (19.8 %) among 470 eligible patients responded to the electronic survey. Responders were older than non-responders. The majority (70.5 %) had symptoms resolved by the time of the survey. Ten (11.4 %) patients had persistent symptoms attributed to long COVID-19. The majority were satisfied with the quality of care (82.3 %) and overall experience (76.0 %) in the infusion clinic. After adjusting for gender, comorbidity score, and WHO severity scale, the predicted costs for the groups were $16,544 (inpatient) and $9,097 (outpatient) per patient (difference of $7,447; p < .01). An estimate of 1,077 hospital bed-days were made available to other patients as a result of this transition to outpatient., Conclusion: An outpatient remdesivir program that allowed for early dismissal was perceived favorably by patients. The program resulted in significant cost and resource savings, the latter in terms of the availability of hospital beds for other patients needing critical services., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Raymund R. Razonable reports financial support was provided by Gilead. RRR received research funds from Regeneron and Roche on projects unrelated to this study, as member of the DSMB for Novartis, and is on the American Society of Transplantation Board of Directors. CGR has served as member of advisory board for Gilead Inc. BJB is a Boehringer Ingelheim and Exact Sciences Corporation consultant on unrelated projects. Others declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Potential conflicts of interest. L. M. B.: UpToDate, Inc (royalty payments–authorship duties), Boston Scientific (consultant duties). M. R. S.: Medtronic (research funding, honoraria/consulting fees), Philips (honoraria/consulting fee), AngioDynamics (honoraria/consulting fee). B. R. P.: Armor Health (consulting fee). M. M.: CERTITUDE registry, BIOTRONIK Inc (steering committee member); Boston Scientific (research funding). All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Nocardia often causes pulmonary infection among those with chronic pulmonary disease or immunocompromising conditions. Trimethoprim-sulfamethoxazole (TMP-SMX) is recommended as first-line treatment, though little data exists regarding outcomes of different dosing regimens., Methods: We performed a multicenter retrospective cohort study of adult patients with non-disseminated pulmonary nocardiosis initially treated with TMP-SMX monotherapy. Patients' initial TMP-SMX dosing was categorized as high- (> 10 mg/kg/day), intermediate- (5-10 mg/kg/day) or low-dose (< 5 mg/kg/day). Outcomes included one-year mortality, post-treatment recurrence, and dose adjustment or early discontinuation of TMP-SMX. SMX serum concentrations and their effect on management were also assessed. Inverse probability of treatment weighting was applied to Cox regression analyses., Results: Ninety-one patients were included with 24 (26.4%), 37 (40.7%), and 30 (33.0%) treated with high-, intermediate-, and low-dose TMP-SMX, respectively. Patients who initially received low-dose (HR 0.07, 95% CI 0.01-0.68) and intermediate-dose TMP-SMX (HR 0.27, 95% CI 0.07-1.04) had lower risk of one-year mortality than the high-dose group. Risk of recurrence was similar between groups. Nineteen patients had peak SMX serum concentrations measured which resulted in 7 (36.8%) dose changes and was not associated with one-year mortality or recurrence. However, 66.7% of the high-dose group required TMP-SMX dose adjustment/discontinuation compared to 24.3% of the intermediate-dose and 26.7% of the low-dose groups (p = 0.001)., Conclusions: Low- and intermediate-dose TMP-SMX for non-disseminated pulmonary nocardiosis were not associated with poor outcomes compared to high-dose therapy, which had a higher rate of dose adjustment/early discontinuation. Historically used high-dose TMP-SMX may not be necessary for management of isolated pulmonary nocardiosis., (© 2024. The Author(s).)

Background and Aim: Renal dysfunction is associated with poor outcomes in patients with coronavirus disease 2019 (COVID-19). In an effort to improve outcomes, intravenous remdesivir has been broadly used for the treatment of COVID-19 even in patients with low estimated glomerular filtration rate (eGFR). Our study assessed the residual risk of outcomes of patients with low eGFR despite treatment with remdesivir for COVID-19, during a timeframe prior to the expanded label across all levels of renal function., Methods: We conducted an observational, retrospective, multi-site cohort study of adults hospitalized with COVID-19 treated with at least one dose of remdesivir between November 6, 2020, and November 5, 2021. Electronic medical records were reviewed to obtain patient characteristics, related laboratory data, and outcomes. The primary endpoint was all-cause mortality by day 28. Multivariable logistic regression was used to evaluate association between groups., Results: The study population consisted of 3024 patients hospitalized with COVID-19 and treated with remdesivir. The median age was 67 [IQR 55, 77] years; 42.7% were women, and 88.6% were white. The median eGFR was 76.6 mL/min/1.73 m2 [IQR 52.5, 95.2]; the majority (67.2%) of patients had an eGFR ≥ 60, while 9% had an eGFR <30. All-cause mortality by day 28 was 8.7%. All-cause mortality rates were significantly higher among patients with impaired renal function (Odds Ratio [OR] 1.63 for patients with eGFR 30-59; OR 1.46 for eGFR 15-29; OR 2.42 for eGFR <15 and OR 5.44 for patients on dialysis) compared to patients with eGFR ≥60 mL/min/1.73m2., Conclusions: Lower eGFR remains an independent risk factor for mortality in COVID-19 even in patients treated with remdesivir., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gonzalez Suarez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Vascular graft infection (VGI) is one of the most serious complications following arterial reconstructive surgery. VGI has received increasing attention over the past decade, but many questions remain regarding its diagnosis and management. In this review, we describe our approach to VGI through multidisciplinary collaboration and discuss decision-making for challenging presentations. This document will concentrate on VGI that impacts both aneurysms and pseudoaneurysms excluding the ascending thoracic aorta., Competing Interests: Potential conflicts of interest . L. M. B. reports royalty payments (authorship duties) from UpToDate, Inc. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Vascular graft infection (VGI) is one of the most serious complications following arterial reconstructive surgery. VGI has received increasing attention over the past decade, but many questions remain regarding its diagnosis and management. In this review, we describe our approach to VGI through multidisciplinary collaboration and discuss decision making for challenging presentations. This review will concentrate on VGI that impacts both aneurysms and pseudoaneurysms excluding the ascending thoracic aorta., Competing Interests: Potential conflicts of interest. L. M. B. reports royalty payments (authorship duties) from UpToDate, Inc. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to reduce adverse cardiovascular events in patients with type 2 diabetes mellitus, all-cause mortality, and heart failure hospitalization in patients with heart failure, as well as adverse renal outcomes. However, concerns regarding the heightened risk of genitourinary (GU) infections, particularly urinary tract infections, remain a significant barrier to their wider adoption. Addressing these misconceptions using existing evidence is needed to ensure proper risk-benefit assessment and optimal utilization of this efficacious therapy. This review aims to provide a balanced perspective on the evidence-based cardiovascular and renal benefits of SGLT2is and the associated risk of GU infections. We also summarize and propose clinical practice considerations for SGLT2i-associated GU infections focusing on patients with cardiovascular disease., Competing Interests: Funding Support and Author Disclosures Dr Cox has received grants from AstraZeneca; and has received personal fees from Abiomed, ROCHE, and Translational Catalyst. Dr Lindenfeld is a consultant for Abbott, ADI, Alleviant, Amgen, AstraZeneca, Axon, Boston Scientific, Cordio, CVRx, Cytokinetics, Edwards Lifesciences, Medtronic, Merck, VWave, Vascular Dynamics, Vectorious, and Whiteswell; and has received grants from Analog Devices Inc, AstraZeneca, and Volumetrix. Dr Mentz has received research support and honoraria from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Eli Lilly, Medtronic, Medable, Merck, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Relypsa, Respicardia, Roche, Rocket Pharmaceuticals, Sanofi, Verily, Vifor, Windtree Therapeutics, and Zoll. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Cardiac implantable electronic device-related infective endocarditis (CIED-IE) encompasses a range of clinical syndromes, including valvular, device lead, and bloodstream infections. However, accurately diagnosing CIED-IE remains challenging owing in part to diverse clinical presentations, lack of standardized definition, and variations in guideline recommendations. Furthermore, current diagnostic modalities, such as transesophageal echocardiography and [ 18 F]-fluorodeoxyglucose positron emission tomography-computed tomography have limited sensitivity and specificity, further contributing to diagnostic uncertainty. This can potentially result in complications and unnecessary costs associated with inappropriate device extraction. Six hypothetical clinical cases that exemplify the diverse manifestations of CIED-IE are addressed herein. Through these cases, we highlight the importance of optimizing diagnostic accuracy and stewardship, understanding different pathogen-specific risks for bloodstream infections, guiding appropriate device extraction, and preventing CIED-IE, all while addressing key knowledge gaps. This review both informs clinicians and underscores crucial areas for future investigation, thereby shedding light on this complex and challenging syndrome., Competing Interests: Funding Support and Author Disclosures Dr Baddour has received royalty payments from and served authorship duties for UpToDate; and has served as a consultant for Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Studies conducted prior to SARS-CoV-2 Omicron demonstrated that sotrovimab and remdesivir reduced hospitalization among high-risk outpatients with mild to moderate COVID-19. However, their effectiveness has not been directly compared. This study examined all high-risk outpatients with mild to moderate COVID-19 who received either remdesivir or sotrovimab at Mayo Clinic during the Omicron BA.1 surge from January to March 2022. COVID-19-related hospitalization or death within 28 days were compared between the two treatment groups. Among 3257 patients, 2158 received sotrovimab and 1099 received remdesivir. Patients treated with sotrovimab were younger and had lower comorbidity but were more likely to be immunocompromised than remdesivir-treated patients. The majority (89%) had received at least one dose of COVID-19 vaccine. COVID-19-related hospitalization (1.5% and 1.0% in remdesivir and sotrovimab, respectively, p = .15) and mortality within 28 days (0.4% in both groups, p = .82) were similarly low. A propensity score weighted analysis demonstrated no significant difference in the outcomes between the two groups. We demonstrated favorable outcomes that were not significantly different between patients treated with remdesivir or sotrovimab., (© 2024. The Author(s).)

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., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Given the challenges of conventional therapies in managing right-sided infective endocarditis (RSIE), percutaneous mechanical aspiration (PMA) of vegetations has emerged as a novel treatment option. Data on trends, characteristics, and outcomes of PMA, however, have largely been limited to case reports and case series., Aims: The aim of the current investigation was to provide a descriptive analysis of PMA in the United States and to profile the frequency of PMA with a temporal analysis and the patient cohort., Methods: The International Classification of Diseases, 10th Revision codes were used to identify patients with RSIE in the national (nationwide) inpatient sample (NIS) database between 2016 and 2020. The clinical characteristics and temporal trends of RSIE hospitalizations in patients who underwent PMA was profiled., Results: An estimated 117,955 RSIE-related hospital admissions in the United States over the 5-year study period were estimated and 1675 of them included PMA. Remarkably, the rate of PMA for RSIE increased 4.7-fold from 2016 (0.56%) to 2020 (2.62%). Patients identified with RSIE who had undergone PMA were young (medial age 36.5 years) and had few comorbid conditions (median Charlson Comorbidity Index, 0.6). Of note, 36.1% of patients had a history of hepatitis C infection, while only 9.9% of patients had a cardiovascular implantable electronic device. Staphylococcus aureus was the predominant (61.8%) pathogen. Concomitant transvenous lead extraction and cardiac valve surgery during the PMA hospitalization were performed in 18.2% and 8.4% of admissions, respectively. The median hospital stay was 19.0 days, with 6.0% in-hospital mortality., Conclusions: The marked increase in the number of PMA procedures in the United States suggests that this novel treatment option has been embraced as a useful tool in select cases of RSIE. More work is needed to better define indications for the procedure and its efficacy and safety., (© 2024 Wiley Periodicals LLC.)

In this clinicopathological conference, invited experts discussed a previously published case of a patient with nonischemic cardiomyopathy who underwent heart transplantation from a genetically modified pig source animal. His complex course included detection of porcine cytomegalovirus by plasma microbial cell-free DNA and eventual xenograft failure. The objectives of the session included discussion of selection of immunosuppressive regimens and prophylactic antimicrobials for human xenograft recipients, description of infectious disease risk assessment and mitigation in potential xenograft donors and understanding of screening and therapeutic strategies for potential xenograft-related infections., (© 2023 Wiley Periodicals LLC.)

Background: Limited research has focused on bloodstream infection (BSI) in patients with arterial grafts. This study aims to describe the incidence and outcomes of BSI after arterial aneurysm repair in a population-based cohort., Methods: The expanded Rochester Epidemiology Project (e-REP) was used to analyze aneurysm repairs in adults (aged ≥18 years) residing in 8 counties in southern Minnesota from January 2010 to December 2020. Electronic records were reviewed for the first episode of BSI following aneurysm repair. BSI patients were assessed for vascular graft infection (VGI) and followed for all-cause mortality., Results: During the study, 643 patients had 706 aneurysm repairs: 416 endovascular repairs (EVARs) and 290 open surgical repairs (OSRs). Forty-two patients developed BSI during follow-up. The 5-year cumulative incidence of BSI was 4.7% (95% confidence interval [CI], 3.0%-6.4%), with rates of 4.0% (95% CI, 1.8%-6.2%) in the EVAR group and 5.8% (95% CI, 2.9%-8.6%) in the OSR group ( P = .052). Thirty-nine (92.9%) BSI cases were monomicrobial, 33 of which were evaluated for VGI. VGI was diagnosed in 30.3% (10/33), accounting for 50.0% (8/16) of gram-positive BSI cases compared to 11.8% (2/17) of gram-negative BSI cases ( P = .017). The 1-, 3-, and 5-year cumulative post-BSI all-cause mortality rates were 22.2% (95% CI, 8.3%-34.0%), 55.8% (95% CI, 32.1%-71.2%), and 76.8% (95% CI, 44.3%-90.3%), respectively., Conclusions: The incidence of BSI following aneurysm repair was overall low. VGI was more common with gram-positive compared to gram-negative BSI. All-cause mortality following BSI was high, which may be attributed to advanced age and significant comorbidities in our cohort., Competing Interests: Potential conflicts of interest. L. M. B. has received royalty payments (authorship duties) from UpToDate and has served as a consultant for Boston Scientific. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The literature regarding Clostridioides difficile infection (CDI) in left ventricular assist devices (LVADs) patients is limited. Therefore, we aimed to characterize the clinical course, risk factors, management, and outcomes of LVAD patients who developed CDI. Adult patients who underwent LVAD placement during 2010-2022 and developed CDI were included. To determine risk factors and outcomes, we matched CDI patients with LVAD patients who did not develop CDI. Each CDI case was matched with up to two control subjects by age, sex, and time from LVAD implantation. Forty-seven of 393 LVAD patients (12.0%) developed CDI. The median time from LVAD implantation to CDI was 147 days (interquartile range 22.5-647.0). The most common CDI treatment was oral vancomycin (n = 26, 55.3%). Thirteen patients (27.7%) required treatment extension because of a lack of clinical response. Three patients (6.4%) developed recurrent CDI. When 42 cases were matched to 79 control subjects, antibiotic exposure within 90 days was significantly associated with CDI (adjusted odds ratio 5.77; 95% confidence interval, 1.87-17.74; p = 0.002). Moreover, CDI was associated with 1 year mortality (adjusted hazard ratio 2.62; 95% confidence interval, 1.18-5.82; p = 0.018). This infection occurs most often within the first year after LVAD implantation and was associated with 1 year mortality. Antibiotic exposure is an important risk for CDI., Competing Interests: Disclosure: S.D.S. received consulting fees from Abbot and Medtronic. R.R.R. received grants (funds to the institution) from Gilead, Roche, Regeneron. He is a member of the Data Safety Monitoring Board (Novartis) and Endpoint Adjudication Committee (Allovir) and the Board of Directors of the American Society of Transplantation. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Background: Specific pretransplant infections have been associated with poor posttransplant outcomes. However, the impact of pretransplant Nocardia isolation has not been studied., Methods: We 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., Results: Nine 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., Conclusions: This 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., (© 2023 Wiley Periodicals LLC.)

(1) Background: Coagulase-negative staphylococci (CoNS) are an important group of organisms that can cause bloodstream infection (BSI) and infective endocarditis (IE). The prevalence of IE in patients with BSI due to different CoNS species, however, has received limited attention; (2) Methods: A retrospective study of adults with monomicrobial CoNS BSI who had undergone echocardiography and a risk factor analysis was done to determine the most common CoNS species that cause definite IE; (3) Results: 247 patients with CoNS BSI were included in the investigation; 49 (19.8%) had definite IE, 124 (50.2%) possible IE, and 74 (30.0%) BSI only. The latter two entities were grouped in one category for further analysis. The most common species in CoNS BSI was Staphylococcus epidermidis (79.4%) and most patients (83.2%) had possible IE/BSI only. 59.1% of patients with BSI due to S. lugdunensis had definite IE. The majority of CoNS were healthcare-associated/nosocomial bacteremia. Multivariable analysis demonstrated that valve disease ( p = 0.002) and a foreign cardiovascular material ( p < 0.001) were risk factors associated with definite IE. Patients with S. lugdunensis BSI had an 8-fold higher risk of definite IE than did those with S. epidermidis BSI and nearly a 13-fold higher risk than did patients with BSI due to other species of CoNS ( p = 0.002); (4) Conclusions: The prevalence of definite IE in patients with BSI due to different CoNS species was significant. CoNS bacteremia, particularly with S. lugdunensis , confers a significant risk of IE, particularly in patients with a valve disease or intravascular foreign body material and should not be immediately dismissed as a contaminant.

Background: Nocardia is an opportunistic pathogen that primarily affects immunocompromised individuals, including solid organ transplant (SOT) recipients. Up to 2.65% of SOT recipients develop nocardiosis; however, few studies have examined risk factors and prophylaxis for nocardiosis., Methods: We performed a multicenter, matched nested case-control study of adult SOT recipients with culture-confirmed nocardiosis from 2000 through 2020. Controls were matched up to 2:1 by sex, first transplanted organ, year of transplant, transplant center, and adequate post-transplant follow-up. Multivariable conditional logistic regression was performed to analyze associations with nocardiosis. Cox proportional hazards regression compared 12-month mortality between infection and uninfected patients., Results: One hundred and twenty-three SOT recipients were matched to 245 uninfected controls. Elevated calcineurin inhibitor level, acute rejection, cytomegalovirus infection, lymphopenia, higher prednisone dose, and older age were significantly associated with nocardiosis while trimethoprim-sulfamethoxazole prophylaxis was protective (odds ratio [OR] .34; 95% confidence interval [CI] .13-.84). The effect of prophylaxis was similar, though not always statistically significant, in sensitivity analyses that only included prophylaxis dosed more than twice-per-week (OR .30; 95% CI .11-.80) or restricted to years 2015-2020 (OR .33, 95% CI .09-1.21). Nocardiosis was associated with increased 12-month mortality (hazard ratio 5.47; 95% confidence interval 2.42-12.35)., Conclusions: Multiple measures of immunosuppression and lack of trimethoprim-sulfamethoxazole prophylaxis were associated with nocardiosis in SOT recipients. Effectiveness of prophylaxis may be related to trimethoprim-sulfamethoxazole dose or frequency. Trimethoprim-sulfamethoxazole should be preferentially utilized over alternative agents in SOT recipients with augmented immunosuppression or signs of heightened immunocompromise., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To describe the incidence, epidemiology, and outcomes of vascular graft infection (VGI) in a population-based study in southern Minnesota., Patients and Methods: Retrospective review of all adult patients from 8 counties who underwent arterial aneurysm repair between January 1, 2010, and December 31, 2020. Patients were identified through the expanded Rochester Epidemiology Project. The Management of Aortic Graft Infection Collaboration criteria were used to define VGI., Results: A total of 643 patients underwent 708 aneurysm repairs: 417 endovascular (EVAR) and 291 open surgical (OSR) repairs. Of these patients, 15 developed a VGI during median follow-up of 4.1 years (interquartile range, 1.9-6.8 years), corresponding to a 5-year cumulative incidence of 1.6% (95% CI, 0.6% to 2.7%). The cumulative incidence of VGI 5 years after EVAR was 1.4% (95% CI, 0.2% to 2.6%) compared with 2.0% (95% CI, 0.3% to 3.7%) after OSR (P=.843). Of the 15 patients with VGI, 12 were managed conservatively without explantation of the infected graft/stent. Ten died during median follow-up from VGI diagnosis of 6.0 years (interquartile range, 5.5-8.0 years), including 8 of the 12 patients treated conservatively., Conclusion: The VGI incidence in this study was overall low. There was no statistically significant difference in VGI incidence after OSR and EVAR. The all-cause mortality rate after VGI was high and reflected an older cohort with multiple comorbid conditions., (Copyright © 2023 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

The prevalence of invasive candidiasis caused by non- Candida albicans has rapidly increased. Candida glabrata ( Nakaseomyces glabrata ) is an important pathogen associated with substantial mortality. Our study examined the antifungal temporal susceptibility of C. glabrata and cross-resistance/non-wild-type patterns with other azoles and echinocandins. Laboratory data of all adult patients with C. glabrata isolated from clinical specimens at the Mayo Clinic, Rochester, from 2012 to 2022 were collected. Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints were used. We obtained 1046 C. glabrata isolates from 877 patients. Using CLSI and EUCAST breakpoints, 187 (17.9%) isolates and 256 (24.5%) isolates were fluconazole-resistant, respectively. Focusing on C. glabrata bloodstream infections, fluconazole-resistance ranged from 16 to 22%. Among those 187 fluconazole-resistant isolates, 187 (100%) and 184 (98.4%) isolates were also voriconazole and posaconazole non-wild-type, respectively, with 97 (51.9%) isolates deemed non-wild type for itraconazole. The fluconazole susceptibility pattern has not changed over the past decade. The proportion of fluconazole-resistant C. glabrata is relatively high, which could be due to the complexity of patients and fluconazole exposure. Itraconazole appears to be a compelling step-down therapy for fluconazole-resistant C. glabrata , given the high proportion of wild-type isolates. Further research to examine clinical outcomes is warranted.

Posaconazole therapeutic drug monitoring (TDM) is widely utilized to assess therapeutic efficacy and safety; however, clinical effects of very high serum concentrations are unknown. A retrospective review of 90 patients receiving posaconazole for treatment or prophylaxis of invasive fungal infections with serum concentrations ≥3000 ng/mL from 1/1/2019 to 4/30/2021 evaluated the incidence and type of adverse drug reactions (ADRs). Symptomatic ADRs were very common in patients with posaconazole concentrations of ≥5000 ng/mL and 3000-4999 ng/mL (80% vs. 58.8%; P = 0.31). Posaconazole TDM should be performed for both treatment and prophylaxis indications and dose decrease for serum concentrations >3000 ng/mL should be considered., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

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., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Purpose of Review: Bloodstream infection (BSI) in patients with cardiac implantable electronic devices (CIEDs) is common and can prompt challenges in defining optimal management. We provide a contemporary narrative review of this topic and propose a pathogen-dependent clinical approach to patient management., Recent Findings: BSI due to staphylococci, viridans group streptococci, and enterococci is associated with an increased risk of underlying CIED infection, while the risk of CIED infection due to other organisms is poorly defined. There is growing evidence that positron emission tomography-computed tomography may be helpful in some patients with BSI and underlying CIED. Twenty studies were included to examine the impact of microbiologic findings on the risk of CIED infection among patients with BSI. Diagnosis of CIED infection in patients with BSI without pocket findings is often difficult, necessitating the use of novel diagnostic tools to help guide the clinician in subsequent patient management., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pancreatic fungal infection (PFI) in patients with necrotizing pancreatitis can lead to significant morbidity and mortality. The incidence of PFI has increased during the past decade. Our study aimed to provide contemporary observations on the clinical characteristics and outcomes of PFI in comparison to pancreatic bacterial infection and necrotizing pancreatitis without infection. We conducted a retrospective study of patients with necrotizing pancreatitis (acute necrotic collection or walled-off necrosis), who underwent pancreatic intervention (necrosectomy and/or drainage) and had tissue/fluid culture between 2005 and 2021. We excluded patients with pancreatic procedures prior to hospitalization. Multivariable logistic and Cox regression models were fitted for in-hospital and 1-year survival outcomes. A total of 225 patients with necrotizing pancreatitis were included. Pancreatic fluid and/or tissue was obtained from endoscopic necrosectomy and/or drainage (76.0%), CT-guided percutaneous aspiration (20.9%), or surgical necrosectomy (3.1%). Nearly half of the patients had PFI with or without concomitant bacterial infection (48.0%), while the remaining patients had either bacterial infection alone (31.1%) or no infection (20.9%). In multivariable analysis to assess the risk of PFI or bacterial infection alone, only previous pancreatitis was associated with an increased odds of PFI vs. no infection (OR 4.07, 95% CI 1.13-14.69, p = .032). Multivariable regression analyses revealed no significant differences in in-hospital outcomes or one-year survival between the 3 groups. Pancreatic fungal infection occurred in nearly half of necrotizing pancreatitis. Contrary to many of the previous reports, there was no significant difference in important clinical outcomes between the PFI group and each of the other two groups., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

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. We conducted a retrospective study of adults with beta-hemolytic streptococcal BSI from a primary skin/soft tissue source from 2015 to 2020. Patients transitioned to oral antibiotics within 7 days of treatment initiation were compared to those who continued intravenous therapy, after propensity score matching. The primary outcome was 30-day treatment failure (composite of mortality, infection relapse, and hospital readmission). A prespecified 10% noninferiority margin was used for the primary outcome. We identified 66 matched pairs of patients treated with oral and intravenous antibiotics as definitive therapy. Based on an absolute difference in 30-day treatment failure of 13.6% (95% confidence interval 2.4 to 24.8%), the noninferiority of oral therapy was not confirmed ( P  = 0.741); on the contrary, the superiority of intravenous antibiotics is suggested by this difference. Acute kidney injury occurred in two patients who received intravenous treatment and zero who received oral therapy. No patients experienced deep vein thrombosis or other vascular complications related to treatment. In patients treated for beta-hemolytic streptococcal BSI, those who transitioned to oral antibiotics by day 7 showed higher rates of 30-day treatment failure than propensity-matched patients. This difference may have been driven by underdosing of oral therapy. Further investigation into optimal antibiotic choice, route, and dosing for definitive therapy of BSI is needed., Competing Interests: The authors declare a conflict of interest. A.V. reports being an inventor for Mayo Clinic Travel App interaction with Smart Medical Kit and Medical Kit for Pilgrims and receiving funding from Moderna Inc for Advisory Board participation. All other authors have no potential conflicts of interest to report.

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., Competing Interests: Potential conflicts of interest. LMB reports the following: royalty payments—authorship duties from UpToDate, Inc.; consultant duties for Boston Scientific; and consultant duties for Roivant Sciences. MRS reports the following: research funding and honoraria/consulting fees from Medtronic; and honoraria/consulting fee from Spectranetics, Boston Scientific, and Philips. BRP reports consulting fees from Armor Health. MM reports the following: consulting for Convatec, Biotronik Inc., and Biosense Webster; and research funding from Boston Scientific. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Central nervous system (CNS) phaeohyphomycosis is a rare and often fatal fungal infection. Our study reported a case series of eight CNS phaeohyphomycosis cases at our institution over the past 20 years. We did not observe the common pattern of risk factors, abscess location, or number of abscesses among them. Most patients were immunocompetent without classic risk factors for fungal infection. Early diagnosis and aggressive management with surgical intervention and prolonged antifungal therapy can lead to a favorable outcome. The study highlights the need for further research to better understand the pathogenesis and optimal management of this challenging rare infection., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Introduction: During the early phase of the coronavirus disease 2019 (COVID-19), remdesivir was only approved for hospitalized patients. Our institution developed hospital-based, outpatient infusion centers for selected hospitalized patients with COVID-19 who had clinical improvement to allow for early dismissal. The outcomes of patients who transitioned to complete remdesivir in the outpatient setting were examined., Methods: Retrospective study of all hospitalized adult patients with COVID-19 who received at least one dose of remdesivir from November 6, 2020, to November 5, 2021, at one of the Mayo Clinic hospitals., Results: Among 3029 hospitalized patients who received treatment with remdesivir for COVID-19, the majority (89.5%) completed the recommended 5-day course. Among them, 2169 (80%) patients completed treatment during hospitalization, whereas 542 (20.0%) patients were dismissed to complete remdesivir in outpatient infusion centers. Patients who completed the treatment in the outpatient setting had lower odds of death within 28 days (aOR 0.14, 95% CI 0.06-0.32, p  < 0.001). However, their rate of subsequent hospital encounters within 30 days was higher (aHR 1.88, 95% CI 1.27-2.79, p  = 0.002). Among patients treated with remdesivir only in the inpatient setting, the adjusted odds of death within 28 days were significantly higher among those who did not complete the 5-day course of remdesivir (aOR 2.07, 95% CI 1.45-2.95, p  < 0.001)., Conclusions: This study describes the clinical outcomes of a strategy of transitioning remdesivir therapy from inpatient to outpatient among selected patients. Mortality was lower among patients who completed the 5-day course of remdesivir., Competing Interests: RRR received research funds from Regeneron and Roche on projects not related to this study, as a member of the DSMB for Novartis and is on the Board of Directors of the American Society of Transplantation. CGR is a member of an advisory board for Gilead. All other authors declare no potential conflicts of interest., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: Current guidelines recommend immunomodulators, tocilizumab or baricitinib, for the management of severe coronavirus disease-2019 (COVID-19) in patients with increasing oxygen requirements. Given their immunosuppressive effects, there is a concern for higher rates of infection among transplant recipients., Methods: A retrospective cohort study of transplant patients with severe COVID-19 between April 2020 and January 2022 was performed at the Mayo Clinic. The primary outcome was incidence of secondary infections after COVID-19 diagnosis. Secondary outcomes were 90-day mortality, ventilatory days, and thromboembolic events., Results: A total of 191 hospitalized transplant patients were studied, including 77 (40.3%) patients who received an immunomodulator. Overall, 89% were solid organ transplant recipients, with kidney as the most common transplanted organ (50.3%). The majority (89.0%) required oxygen supplementation on admission, and 39.8% of these patients required mechanical ventilation during the hospital course. There was no significant difference in the incidence of secondary infections between those who received or did not receive an immunomodulator (p = .984). Likewise, there was no difference in 90-day mortality between patients who received or did not receive an immunomodulator (p = .134). However, higher mortality was observed among patients that developed a secondary infection (p < .001)., Conclusion: The use of immunomodulators in transplant patients with severe COVID-19 was not significantly associated with an increased risk of secondary infections. Secondary infections were associated with higher risk of all-cause mortality. Future studies of larger cohorts are needed to explore the effect of immunomodulators on survival among transplant patients with COVID-19., (© 2023 Wiley Periodicals LLC.)

Methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia is associated with poor outcomes. Ceftriaxone offers logistical advantages over other standard therapies, though in vitro studies have questioned its efficacy and clinical studies of ceftriaxone in MSSA bacteremia are conflicting.We performed a multicenter, retrospective cohort study of adult patients who received ceftriaxone, cefazolin, or antistaphylococcal penicillins as definitive therapy for MSSA bacteremia from 2018 to 2019. Definitive therapy was defined as the antibiotic used in the outpatient setting. Patients were excluded if they received less than 7 days of outpatient therapy. Follow-up started on the date of definitive therapy completion. The primary outcome was 90-day treatment failure, defined as a composite of mortality and microbiologic recurrence. This was analyzed with multivariable Cox regression. A total of 223 patients were included, 37 (16.6%) of whom received ceftriaxone. The most common ceftriaxone dose was 2 g daily (83.8%). The most common primary site of infection was skin/soft tissue (37.2%), unknown (21.1%), and catheter-related (15.2%). Twenty-six (11.7%) developed infective endocarditis. Median total duration of treatment was 31.0 days, and median outpatient duration was 24.0 days. Twenty-six (11.7%) developed 90-day treatment failure. After adjusting for Charlson comorbidity index, duration of therapy, and use of transesophageal echocardiography, definitive treatment with ceftriaxone was associated with treatment failure (hazard ratio 2.66, 95% confidence interval 1.15-6.12; p=0.022). Among patients with MSSA bacteremia, definitive treatment with ceftriaxone was associated with a higher risk of treatment failure within 90 days as compared to cefazolin or antistaphylococcal penicillins., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Deep brain stimulator (DBS)-related infection is a recognized complication that may significantly alter the course of DBS therapy. We describe the Mayo Clinic Rochester experience with DBS-related infections., Methods: This was a retrospective study of all adults (≥18 years old) who underwent DBS-related procedures between 2000 and 2020 at the Mayo Clinic Rochester., Results: There were 1087 patients who underwent 1896 procedures. Infection occurred in 57/1112 (5%) primary DBS implantations and 16/784 (2%) revision surgeries. The median time to infection (interquartile range) was 2.1 (0.9-6.9) months. The odds of infection were higher with longer operative length ( P = .002), higher body mass index (BMI; P = .006), male sex ( P = .041), and diabetes mellitus ( P = .002). The association between infection and higher BMI ( P = .002), male sex ( P = .016), and diabetes mellitus ( P = .003) remained significant in a subgroup analysis of primary implantations but not revision surgeries. Infection was superficial in 17 (23%) and deep in 56 (77%) cases. Commonly identified pathogens were Staphylococcus aureus (65%), coagulase-negative staphylococci (43%), and Cutibacterium acnes (45%). Three device management approaches were identified: 39 (53%) had complete device explantation, 20 (27%) had surgical intervention with device retention, and 14 (19%) had medical management alone. Treatment failure occurred in 16 (23%) patients. Time-to-event analysis showed fewer treatment failures with complete device explantation ( P = .015). Only 1 individual had complications with brain abscess at failure., Conclusions: Primary DBS implantations had higher rates of infection compared with revision surgeries. Complete device explantation was favored for deep infections. However, device salvage was commonly attempted and is a reasonable approach in select cases given the low rate of complications., Competing Interests: Potential conflicts of interest. Hussam Tabaja: no conflict. Jason Yuen: no conflict. Don Bambino Geno Tai: no conflict. Cristina Corsini Campioli: no conflict. Supavit Chesdachai: no conflict. Daniel C. DeSimone: no conflict. Anhar Hassan: no conflict. Bryan T. Klassen: no conflict. Kai J. Miller: no conflict. Kendall H. Lee: stockholder and board member of NaviNetics. Maryam Mahmood: no conflict. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Cardiovascular implantable electronic device (CIED) infection carries significant morbidity and mortality with bacteremia being a possible marker of device infection. A clinical profile of non- Staphylococcus aureus gram-positive cocci (non-SA GPC) bacteremia in patients with CIED has been limited., Objective: To examine characteristics of patients with CIED who developed non-SA GPC bacteremia and risk of CIED infection., Methods: We reviewed all patients with CIED who developed non-SA GPC bacteremia at the Mayo Clinic between 2012 and 2019. The 2019 European Heart Rhythm Association Consensus Document was used to define CIED infection., Results: A total of 160 patients with CIED developed non-SA GPC bacteremia. CIED infection was present in 90 (56.3%) patients, in whom 60 (37.5%) were classified as definite and 30 (18.8%) as possible. This included 41 (45.6%) cases of coagulase-negative Staphylococcus (CoNS), 30 (33.3%) cases of Enterococcus , 13 (14.4%) cases of viridans group streptococci (VGS), and 6 (6.7%) cases of other organisms. The adjusted odds of CIED infection in cases due to CoNS, Enterococcus , and VGS bacteremia were 19-, 14-, and 15-fold higher, respectively, as compared with other non-SA GPC. In patients with CIED infection, the reduction in risk of 1-year mortality associated with device removal was not statistically significant (hazard ratio 0.59; 95% confidence interval 0.26-1.33; P = .198)., Conclusions: The prevalence of CIED infection in non-SA GPC bacteremia was higher than previously reported, particularly in cases due to CoNS, Enterococcus species, and VGS. However, a larger cohort is needed to demonstrate the benefit of CIED extraction in patients with infected CIED due to non-SA GPC., (© 2022 Heart Rhythm Society. Published by Elsevier Inc.)

Blood cultures have been the gold standard for identifying pathogens in infective endocarditis (IE). Blood culture-negative endocarditis (BCNE), however, occurs in 40% or more of IE cases with the bulk of them due to recent antibiotic exposure prior to obtaining blood cultures. Increasingly, molecular techniques are being used for pathogen identification in cases of BCNE and more recently has included metagenomic next-generation sequencing (mNGS). We therefore performed a literature search on August 31, 2022, that assessed the mNGS in IE and 13 publications were identified and included in a systematic review. Eight (61.5%) of them focused only on IE with mNGS performed on cardiac valve tissue in four studies, plasma in three studies and cardiac implantable electronic devices (CIED) in one study. Gram-positive cocci, including Staphylococcus aureus (n = 31, 8.9%), coagulase-negative staphylococci (n = 61, 17.6%), streptococci (n = 130, 37.5%), and Enterococcus faecalis (n = 23, 6.6%) were the predominant organisms identified by mNGS. Subsequent investigations are needed to further define the utility of mNGS in BCNE and its impact on patient outcomes. Despite some pitfalls, mNGS seems to be of value in pathogen identification in IE cases, particularly in those with BCNE. This study was registered and on the Open Science Framework platform.

Objective: To estimate the incidence of invasive pneumococcal disease (IPD) in the pre-13-valent pneumococcal conjugate vaccine (pre-PCV13; 7-valent pneumococcal conjugate vaccine era, 2002-2010) and post-PCV13 (2011-2018) time periods., Patients and Methods: Using the Rochester Epidemiology Project, we conducted a population-based cohort study of all IPD cases in Olmsted County, Minnesota, from January 1, 2002, to December 31, 2018., Results: Overall, 187 cases of IPD were identified. The incidence of IPD decreased significantly from 11.1 (95% CI, 9.1 to 13.2) to 5.6 (95% CI, 4.3 to 6.9) per 100,000 person-years when the pre- and post-PCV13 periods (2002-2010 vs 2011-2018) were compared (P<.001). Of the 187 patients with IPD, 112 (59.9%) had previously received at least 1 dose of pneumococcal vaccine. Among the IPD cases in the post-PCV13 period, there was an increase in non-PCV13 serotypes, mainly 11A (from 1.0% [1 of 105] to 6.2% [4 of 64]) and 33F (from 2.9% [3 of 105] to 15.6% [10 of 64]), while PCV13/non-7-valent pneumococcal conjugate vaccine serotypes declined from 38.1% (40 of 105) to 15.6% (10 of 64). At 30 days after an IPD diagnosis, the survival rate was 88.8% (95% CI, 84.4% to 93.4%)., Conclusion: A marked decline in IPD incidence occurred during the post-PCV13 era. Because of the observed increase in non-PCV13 serotypes, coupled with multiple factors that impact the epidemiology of IPD, ongoing surveillance of patients with IPD, particularly due to non-PCV13 serotypes, is warranted., (Copyright © 2022 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Gram-negative bacteremia (GNB) as a manifestation of cardiovascular implantable electronic device (CIED) infection is uncommon. Moreover, echocardiography may be nonspecific in its ability to differentiate whether CIED lead masses are infected. We aimed to determine the rate of CIED infection in the setting of GNB., Methods: All patients with CIED who were hospitalized with GNB during 2012-2019 at Mayo Clinic were investigated. The definition of CIED infection was based on criteria recommended by the 2019 European Heart Rhythm Association document., Results: A total of 126 patients with CIED developed GNB. None of them had signs of pocket infection. Twenty (15.9%) patients underwent transesophageal echocardiography. Overall, 4 (3%) patients had definite CIED infection. None of them underwent CIED extraction; 3 died within 12 weeks and 1 received long-term antibiotic suppression. Ten (8%) patients had possible CIED infection; despite no CIED extraction, no patient had relapsing GNB. We observed a higher rate of CIED infection in patients with Serratia marcescens bacteremia as compared to that in patients with other GNB., Conclusions: The rate of CIED infection following GNB was relatively low. However, accurate classification of CIED infection among patients presenting with GNB remains challenging, in part, due to a case definition of CIED infection that is characterized by a low pretest probability in the setting of GNB. Prospective, multicenter studies are needed to determine accurate identification of CIED infection among GNB, so that only patients with true infection undergo device removal., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: There is insufficient evidence regarding postoperative systemic antibiotic prophylaxis use for more than 24 h following cardiovascular implantable electronic devices (CIED) implantation and its impact on infection prevention. However, this strategy remains a common practice in many institutions., Methods: We conducted a systematic review and meta-analysis including studies that compared the outcomes of patients: (1) who received preoperative plus 24 h or more of postoperative antibiotic prophylaxis (intervention group); and (2) who received either preoperative only or preoperative plus less than 24 h of antibiotic prophylaxis (control group). Risk of bias was assessed with ROBINS-I and ROB-2 tools. Risk ratio (RR) was pooled using random-effect meta-analyses with inverse variance method., Results: Eight studies that included two randomized controlled trials (RCTs) and six cohort studies with a total of 26,187 patients were included in the analysis. Overall, there were no differences in outcomes between the two groups, which included rates of CIED infection (RR 0.77, 95% CI 0.42, 1.42), mortality (RR 1.19, 95% CI 0.69, 2.06), pocket hematoma (RR 1.15, 95% CI 0.44, 3.00) or reintervention (RR 0.87, 95% CI 0.22, 3.46). Of note, the results were primarily impacted by the larger RCT., Conclusions: There was no benefit of postoperative antibiotic prophylaxis for more than 24 h following CIED implantation in the current systematic review and meta-analysis. This supports the practice advocated by current guidelines which foster antibiotic stewardship and may result in reductions of adverse drug events, selection for antibiotic resistance, and financial costs of prolonged postoperative antibiotic prophylaxis., (© 2022 Wiley Periodicals LLC.)

Graft-versus-hostdisease (GVHD) following liver transplantation (LT) is rare but can lead tosignificant mortality. The leading cause of death following GVHD diagnosis isinfectious complications. However, there is a lack of clear descriptions concerning infection and antimicrobial management patterns. Our study aims toprovide the focused details of all infectious complications of acute GVHDfollowing LT. We retrospectively reviewed all adult LT recipients with acute GVHD at Mayo Clinic's Transplant Centers from January 1, 2010, to December 31, 2021. Detailed characteristics of infection in each case were described. Among 4,585 LTs performed during this period, 12 (0.3%) patients developed acuteGVHD. The median time from transplantation to GVHD diagnosis was 49.0 days [IQR 31.5-99.0]. Ten (83.3%) patients developed severe infections leading tomortality. The most common cause of infection was nosocomial bacteremia fromenteric bacteria such as vancomycin-resistant enterococci and gram-negative bacilli. Other infections included breakthrough invasive fungal infections,cytomegalovirus (CMV) reactivation, and Clostridioides difficile colitis. Antimicrobial prophylaxis strategies in most cases were based on the degree of neutropenia-these include levofloxacin for bacterial prophylaxis, nebulized pentamidine for Pneumocystis jiroveci pneumonia prophylaxis, posaconazole for invasive fungal prophylaxis, and valganciclovir based on CMVstatus. All GVHD patients with severe infections succumbed to thesecomplications. Ourstudy reiterates that despite prophylaxis, infectious complications in GVHDfollowing LT are common and lead to exceptionally high mortality. Individualizedantimicrobial treatment, prophylaxis and monitoring strategies remain a criticalcomponent of GVHD management. Further study to optimize these practices isrequired., (© 2022 Wiley Periodicals LLC.)

Introduction: The diagnosis of smear-negative pulmonary tuberculosis (SNPTB) is challenging. Interferon gamma-release assays (IGRAs) may be helpful in early diagnosis among these patients resulting in prompt treatment and favorable outcomes., Methods: We performed a comprehensive search from each databases' inception to April 5, 2021. The studies that provided sufficient data regarding the sensitivity and specificity of IGRAs included QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB, or QuantiFERON-TB Gold Plus for diagnosis of SNPTB were included., Results: Of 1,312 studies screened, 16 studies were included; 11 QFT-GIT, 2 T-SPOT.TB, and 3 QFT-GIT and T-SPOT.TB. For diagnosis of SNPTB, QFT-GIT had sensitivity of 0.77 (95% CI 0.71-0.82), specificity of 0.70 (95% CI 0.58-0.80), diagnostic odds ratio (DOR) of 8.03 (95% CI 4.51-14.31), positive likelihood ratio (LR) of 2.61 (95% CI 1.80-3.80), negative LR of 0.33 (95% CI 0.25-0.42), and area under receiver operating characteristic (AUROC) of 0.81 (95% CI 0.77-0.84). T-SPOT.TB had sensitivity of 0.74 (95% CI 0.71-0.78), specificity of 0.71 (95% CI 0.49-0.86), DOR of 6.96 (95% CI 2.31-20.98), positive LR of 2.53 (95% CI 1.26-5.07), negative LR of 0.36 (95% CI 0.24-0.55), and AUROC of 0.77 (95% CI 0.73-0.80). The specificity seemed lower in the subgroup analyses of studies from high tuberculosis burden counties compared to the studies from low tuberculosis burden., Conclusion: IGRAs do have insufficient diagnostic performance for SNPTB. However, the tests are still helpful to exclude tuberculosis among patients with low pre-test probability. Registry: PROSPERO: CRD42021274653., (© 2022. The Author(s).)

Background: Abiotrophia, Granulicatella, and Gemella are gastrointestinal microbiota, gram-positive cocci that behave like viridans group streptococci. Despite the low incidence of bacteremia from these organisms, they can lead to infective endocarditis (IE) and other clinical syndromes. Due to scant data, we aim to describe detailed clinical features, management, and outcomes of patients with bacteremia from these organisms., Methods: We reviewed all adult patients who developed Abiotrophia, Granulicatella, or Gemella bacteremia from 2011 to 2020, at Mayo Clinic., Results: We identified 238 patients with positive blood culture for these organisms. Of those, 161 (67.6%) patients were deemed to have bacteremia of clinical significance; 62 (38.5%) were neutropenic, - none of whom were diagnosed with IE. The primary source of bacteremia for the neutropenic group was the gastrointestinal tract. Among 161 patients, echocardiography was obtained in 88 (54.7%) patients, especially those with unknown sources of bacteremia. A total of 19 cases had IE: 5 (26.3%) Abiotrophia, 11 (57.9%) Granulicatella, and 3 (15.8%) Gemella. Based on known IE scoring systems, the negative predictive value at established cutoffs for these scores, performed with our cohort were 95.9%, 100% and 97.9% for NOVA, HANDOC and DENOVA scores, respectively. We also found that the penicillin-non-susceptible rate was high in Abiotrophia (66.7%) and Granulicatella (53.7%)., Conclusions: We described unique characteristics of Abiotrophia, Granulicatella, and Gemella bacteremia at our institution. Clinical significance, clinical syndrome, their proclivity of endocarditis, and susceptibility pattern should be thoroughly reviewed when encountering these organisms., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Cardiovascular implantable electronic device (CIED) implantation has markedly increased over the past 2 decades. Staphylococcus aureus bacteremia (SAB) occurs in patients with CIED, and determination of device infection often is difficult., Objectives: The purpose of this study was to examine the rate and clinical characteristics of SAB in patients living with CIED using the 2019 European Heart Rhythm Association (EHRA) international consensus document., Methods: We conducted a retrospective study of patients with CIED who were hospitalized at Mayo Clinic, Rochester, with SAB from 2012 to 2019. Patients who met CIED infection criteria after SAB based on EHRA criteria were identified. A descriptive statistic and time-dependent Cox model were used., Results: Overall, 110 patients with CIED developed SAB, of whom 92 (83.6%) underwent transesophageal echocardiogram (TEE). Fifty-seven (51.8%) and 31 (28.2%) patients met criteria for definite and possible CIED infections, respectively. At 30-day follow-up, the cumulative rate of patients undergoing complete device extraction was 80.0% in the definite CIED infection group, compared with 38.8% and 32.9% in the possible and rejected CIED infection groups, respectively. We found that CIED extraction was associated with an 83% reduction in risk of 1-year mortality in the definite CIED infection group., Conclusion: The rate of CIED infections after SAB was higher than that reported previously. Increased use of TEE and a novel case definition with broader diagnostic criteria likely were operative, in part, in accounting for the higher rate of CIED infections complicating SAB. Complete device removal is critical in patients with definite CIED infection to improve 1-year mortality., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Cardiovascular device infection due to rapidly growing mycobacteria (RGM) is rarely encountered in clinical practice. Due to the increasing number of indications and use of cardiovascular devices in an aging population, optimized management of these infections is of great importance. We report seven cases of RGM cardiovascular device infection. Three patients had left-ventricular assist device (LVAD) infections; two patients had cardiovascular implantable device (CIED) infections; and one had an aortic vascular stent infection. Specific cardiac valvular infection was not detected among any of the patients. All patients had a high number of comorbidities which limited some patients from receiving optimal combination antimicrobial therapy. The prognosis of cardiovascular device infections with RGM is guarded with only four patients still alive; however, the treatment approach for each patient varied considerably and often based on concurrent medical conditions, overall adjustments to goals of care, and specific patient preferences. Further analysis of cardiovascular device infections with RGM is warranted to establish a more systematic approach in successful management., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier Ltd.)

Endogenous endophthalmitis caused by Enterococcus gallinarum , an organism with intrinsic resistance to vancomycin, has rarely been reported. We present a case of persistent E. gallinarum bacteremia in a female recipient of hematopoietic stem cell transplant (HSCT) complicated by endophthalmitis and meningoventriculitis, resulting in a fatal outcome despite treatment with intravenous ampicillin and daptomycin. Treatment of endophthalmitis often presents a challenge due to the lack of options for antimicrobials with reliable ocular penetration. Therapeutic decisions can become particularly complex with the involvement of drug-resistant pathogens and host characteristics that limit the choice of antimicrobials due to drug toxicity. This case illustrates a rare manifestation of an opportunistic pathogen., (Copyright © 2021, Association of Medical Microbiology and Infectious Disease Canada (AMMI Canada).)

Background: Lactic acidosis is a heterogeneous condition with multiple underlying causes and associated outcomes. The use of multi-dimensional patient data to subtype lactic acidosis can personalize patient care. Machine learning consensus clustering may identify lactic acidosis subgroups with unique clinical profiles and outcomes., Methods: We used the Medical Information Mart for Intensive Care III database to abstract electronic medical record data from patients admitted to intensive care units (ICU) in a tertiary care hospital in the United States. We included patients who developed lactic acidosis (defined as serum lactate ≥ 4 mmol/L) within 48 h of ICU admission. We performed consensus clustering analysis based on patient characteristics, comorbidities, vital signs, organ supports, and laboratory data to identify clinically distinct lactic acidosis subgroups. We calculated standardized mean differences to show key subgroup features. We compared outcomes among subgroups., Results: We identified 1919 patients with lactic acidosis. The algorithm revealed three best unique lactic acidosis subgroups based on patient variables. Cluster 1 ( n = 554) was characterized by old age, elective admission to cardiac surgery ICU, vasopressor use, mechanical ventilation use, and higher pH and serum bicarbonate. Cluster 2 ( n = 815) was characterized by young age, admission to trauma/surgical ICU with higher blood pressure, lower comorbidity burden, lower severity index, and less vasopressor use. Cluster 3 ( n = 550) was characterized by admission to medical ICU, history of liver disease and coagulopathy, acute kidney injury, lower blood pressure, higher comorbidity burden, higher severity index, higher serum lactate, and lower pH and serum bicarbonate. Cluster 3 had the worst outcomes, while cluster 1 had the most favorable outcomes in terms of persistent lactic acidosis and mortality., Conclusions: Consensus clustering analysis synthesized the pattern of clinical and laboratory data to reveal clinically distinct lactic acidosis subgroups with different outcomes.

Background: Lactic acidosis is the most common cause of anion gap metabolic acidosis in the intensive care unit (ICU), associated with poor outcomes including mortality. We sought to compare machine learning (ML) approaches versus logistic regression analysis for prediction of mortality in lactic acidosis patients admitted to the ICU., Methods: We used the Medical Information Mart for Intensive Care (MIMIC-III) database to identify ICU adult patients with lactic acidosis (serum lactate ≥4 mmol/L). The outcome of interest was hospital mortality. We developed prediction models using four ML approaches consisting of random forest (RF), decision tree (DT), extreme gradient boosting (XGBoost), artificial neural network (ANN), and statistical modeling with forward stepwise logistic regression using the testing dataset. We then assessed model performance using area under the receiver operating characteristic curve (AUROC), accuracy, precision, error rate, Matthews correlation coefficient (MCC), F1 score, and assessed model calibration using the Brier score, in the independent testing dataset., Results: Of 1919 lactic acidosis ICU patients, 1535 and 384 were included in the training and testing dataset, respectively. Hospital mortality was 30%. RF had the highest AUROC at 0.83, followed by logistic regression 0.81, XGBoost 0.81, ANN 0.79, and DT 0.71. In addition, RF also had the highest accuracy (0.79), MCC (0.45), F1 score (0.56), and lowest error rate (21.4%). The RF model was the most well-calibrated. The Brier score for RF, DT, XGBoost, ANN, and multivariable logistic regression was 0.15, 0.19, 0.18, 0.19, and 0.16, respectively. The RF model outperformed multivariable logistic regression model, SOFA score (AUROC 0.74), SAP II score (AUROC 0.77), and Charlson score (AUROC 0.69)., Conclusion: The ML prediction model using RF algorithm provided the highest predictive performance for hospital mortality among ICU patient with lactic acidosis.

Disseminated blastomycosis in solid organ transplant is uncommon. The diagnosis is usually challenging due to vague clinical presentations, which could lead to a devastating outcome. We reported a unique case of disseminated blastomycosis with laryngeal involvement in a kidney transplant recipient who presented with hoarseness. The diagnosis was made by histopathology and culture of laryngeal mass., (© 2021 Wiley Periodicals LLC.)