Clinical utility of metagenomic next-generation sequencing in fever of undetermined origin.

Background: Metagenomic next-generation sequencing (mNGS) is a novel diagnostic tool increasingly used in the field of infectious diseases. Little guidance is available regarding its appropriate use in different patient populations and clinical syndromes. We aimed to review the clinical utility of mNGS in patients with a specific clinical syndrome and identify factors that may increase its utility. Methods: We retrospectively reviewed charts of 72 non-immunocompromised adults hospitalized with the clinical syndrome of 'fever of undetermined origin' and underwent mNGS testing. Standardized criteria from a previously published study were used to determine the clinical impact of mNGS testing. We applied logistic regression to identify factors associated with a positive clinical impact. Results: Of the 72 patients identified, 62.5% were males with a median age of 56. All patients had a fever at the time of evaluation. At least one organism was identified in 65.3% of cases; most commonly were Epstein-Barr virus (13.9%), cytomegalovirus (12.5%), and Rickettsia typhi (11.1%). Of those determined to have an infectious etiology of their febrile syndrome, 89.5% (n = 34/38) had a positive mNGS. Consistency between the organism(s) on mNGS and the clinically determined infectious etiology was 82.4%. mNGS had a positive clinical impact in 40.3% of cases, a negative impact in 2.8%, and no impact in 56.9% of cases. Besides age, we did not identify other factors associated with a higher likelihood of positive clinical impact. Conclusion: In our review, mNGS had a positive clinical impact in a large proportion of adults with fever of undetermined origin, with minimal negative impact. However, mNGS results should be interpreted carefully given the high rate of detection of pathogens of unclear clinical significance. Randomized clinical trials are needed to assess the clinical utility of this novel diagnostic tool.

Clinical utility of metagenomic next-generation sequencing in fever of undetermined origin In this study, we evaluated the use of a new diagnostic tool, namely, metagenomic next generation sequencing (mNGS), in hospitalized, non-immunocompromised, adult patients with a fever that was otherwise unexplained. We reviewed the clinical utility of this tool in 72 patients and found that at least one organism was found in 65.3% of cases, with the 2 most common organisms being viruses. In patients who were found to have an infection as the cause of their fever, 89.5% had a positive mNGS study. In 82.4% of cases, the infectious organism(s) found on mNGS was the organism thought to be the cause of the fever. Based on definitions from another study, mNGS had a positive clinical impact in 40.3% of cases, a negative impact in 2.8%, and no impact in 56.9% of cases. This study suggests that mNGS has minimal negative impact and can be a useful tool in identifying a causative infectious organism in patients with unexplained fevers. Additional studies are needed to identify patients and clinical conditions that would most benefit from this tool.

Clinical Approach to Evaluation of Underlying Cardiac Device Infection in Patients Hospitalized with Bacteremia.

More than 400,000 cardiac implantable electronic devices (CIEDs), including permanent pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy devices, are implanted every year in the United States (US). Infection is a serious complication of CIED therapy and is associated with high morbidity and mortality. While CIED pocket infection can be diagnosed based on clinical exam findings, positive blood culture may be the only manifestation of CIED lead infection. Thus, management of bacteremia in patients living with CIEDs requires special consideration. This review summarizes contemporary data in the context of the recently updated 2023 Duke-International Society for Cardiovascular Infectious Diseases Criteria for Infective Endocarditis. We have synthesized these data into an algorithmic approach to streamline the diagnostic evaluation of CIED infection in patients presenting with bacteremia.

Candidemia in Patients With Cardiovascular Implantable Electronic Devices: Uncertainty in Management Based on Current International Guidelines.

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.

Bacteremia due to non-Staphylococcus aureus gram-positive cocci and risk of cardiovascular implantable electronic device infection.

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.

Early Lead Extraction for Infected Implanted Cardiac Electronic Devices: JACC Review Topic of the Week.

Infection remains a serious complication associated with the cardiac implantable electronic devices (CIEDs), leading to substantial clinical and economic burden globally. This review assesses the burden of cardiac implantable electronic device infection (CIED-I), evidence for treatment recommendations, barriers to early diagnosis and appropriate therapy, and potential solutions. Multiple clinical practice guidelines recommended complete system and lead removal for CIED-I when appropriate. CIED extraction for infection has been consistently reported with high success, low complication, and very low mortality rates. Complete and early extraction was associated with significantly better clinical and economic outcome compared with no or late extraction. However, significant gaps in knowledge and poor recommendation compliance have been reported. Barriers to optimal management may include diagnostic delay, knowledge gaps, and limited access to expertise. A multipronged approach, including education of all stakeholders, a CIED-I alert system, and improving access to experts, could help bring paradigm shift in the treatment of this serious condition.

Preclinical evaluation of a third-generation absorbable antibacterial envelope.

BACKGROUND: The TYRX (Medtronic) absorbable antibacterial envelope has been shown to stabilize implantable cardiac devices and reduce infection. A third-generation envelope was developed to reduce surface roughness with a redesigned multifilament mesh and enhanced form factor but identical polymer coating and antibiotic concentrations as the currently available second-generation envelope. OBJECTIVE: The purpose of this study was to compare drug elution, bacterial challenge efficacy, stabilization, and absorption of second- vs third-generation envelopes. METHODS: Antibiotic elution was assessed in vitro and in vivo. For efficacy against gram-positive/gram-negative bacteria, 40 rabbits underwent device insertions with or without third-generation envelopes. For stabilization (migration, rotation), 5 sheep were implanted with 6 devices each in second- or third-generation envelopes. Prespecified acceptance criteria were <83-mm migration and <90° rotation. Absorption was assessed via gross pathology. RESULTS: Elution curves were equivalent (similarity factors ≥50 per Food and Drug Administration guidance). Third-generation envelopes eluted antibiotics above minimal inhibitory concentration (MIC) in vivo at 2 hours postimplant through 7 days, consistent with second-generation envelopes. Bacterial challenge showed reductions (P <.05) in infection with second- and third-generation envelopes. Device migration was 5.5 ± 3.5 mm (third-generation) vs 9. 9 ±7.9 mm (second-generation) (P <.05). Device rotation was 18.9° ± 11.4° (third-generation) vs 17.6° ± 15.1° (second-generation) and did not differ (P = .79). Gross pathology confirmed the absence of luminal mesh remainders and no differences in peridevice fibrosis at 9 or 12 weeks. CONCLUSION: The third-generation TYRX absorbable antibacterial envelope demonstrated equivalent preclinical performance to the second-generation envelope. Antibiotic elution curves were similar, elution was above MIC for 7 days, infections were reduced compared to no envelope, and acceptance criteria for migration, rotation, and absorption were met.

Overview and risk factors for postcraniotomy surgical site infection: A four-year experience.

Objective: Despite evidence favoring perioperative antibiotic prophylaxis (ABP) use in patients undergoing craniotomy to reduce rates of surgical site infections (SSIs), standardized protocols are lacking. We describe demographic characteristics, risk factors, and ABP choice in patients with craniotomy complicated with SSI. Design: Retrospective case series from January 1, 2017, through December 31, 2020. Setting: Tertiary-care referral center. Patients: Adults who underwent craniotomy and were diagnosed with an SSI. Methods: Logistic regression to estimate odds ratios and 95% confidence intervals to identify factors associated with SSIs. Results: In total, 5,328 patients undergoing craniotomy were identified during the study period; 59 (1.1%) suffered an SSI. Compared with non-SSI cases, patients with SSI had a significantly higher frequency of emergency procedures: 13.5% versus 5.8% (P = .02; odds ratio [OR], 2.52; 95% confidene interval [CI], 1.10-5.06; P = .031). Patients with SSI had a higher rate of a dirty (5.1% vs 0.9%) and lower rate of clean-contaminated (3.3% vs 14.5%) wound class than those without infection (P = .002). Nearly all patients received ABP before craniotomy (98.3% in the SSI group vs 99.6% in the non-SSI group; P = .10). Combination of vancomycin and cefazolin as dual therapy was more prevalent in the group of patients without infection (n = 1,761, 34.1%) than those with SSI (n = 4, 6.8%) (P < .001), associated with decreased odds for SSI (OR, 0.17; 95% CI, 0.005-0.42; P ≤ .001). Conclusions: SSI are frequently seen after an emergent neurosurgical procedure and a dirty wound classification. Combination of prophylactic cefazolin and vancomycin is associated with decreased risk for SSI.

Predictors of Treatment Failure in Patients With Pyogenic Brain Abscess.

Background: Pyogenic brain abscess poses a significant management challenge to clinicians, hence early diagnosis and interventions are critical. Our objective was to assess predictors of failure of therapy among patients with pyogenic brain abscesses according to surgical versus medical treatment. Methods: Retrospectively reviewed adults with pyogenic brain abscesses at our institution between 2009 and 2020. Treatment was classified as early surgical intervention and no early surgical treatment (medical therapy). Propensity score (PS) adjustment and multivariable regression were used to assess risk of treatment failure from surgical intervention and baseline covariates. Results: A total of 224 patients had pyogenic brain abscess, of whom 106 (47.3%) had early surgical treatment and 118 (52.7%) had medical treatment only. Significant predictors of surgical (vs. medical) treatment included essential hypertension (odds ratio [OR] 95% confidence interval [95% CI] = 2.06 [1.01-4.18]), abscesses number (single vs. multiple, OR [95% CI] =4.81 [1.64-14.08]), midline shift (OR [95% CI] = 3.09 [1.22-7.82]). At 6 months, treatment failure cumulative incidence was 27.1% in the medical group (n = 31) and 21.3% in early surgical group (n = 22). PS-adjusted analysis showed beneficial effect of early surgical treatment (hazard ratio [HR] [95% CI] = 0.55 [0.31-0.98]). Multivariable regression showed similar but statistically nonsignificant estimate of surgical benefit (HR [95% CI] =0.59 [0.34-1.01]; P = 0.056), and significant associations of Charlson Comorbidity Index (CCI) (P = 0.019) and pre-existing central nervous system hardware (P = 0.034) with increased risk of treatment failure. Conclusions: Higher CCI and pre-existing CNS hardware were significant risk factors associated with treatment failure. In propensity-adjusted analysis, early surgery was associated with a 45% reduction in risk of 6-month treatment failure.

The skip phenomenon in Staphylococcus aureus bacteremia: clinical implications.

Serial blood cultures (BCs) are integral in managing Staphylococcus aureus bacteremia (SAB) to determine complication risks and treatment response. Several studies recognized the skip phenomenon (SP)- the occurrence of intermittent negative BCs and recommend obtaining additional BCs to document clearance. We examined patients with SP to determine its clinical significance. Significant differences between those who did and did not manifest the SP included higher rates of injection drug use and community-onset SAB in the SP cohort. Longer SAB duration, high-grade SAB, and complicated bacteremia were more common in the SP group. In unadjusted outcome analyses, association of SP with hospital length of stay was not significant, although a higher risk of in-hospital mortality among SP patients approached significance. Analysis of hospital survivors revealed no significant differences in 90-day relapse or 1-year mortality. Clinical implications of patients with SAB and SP indicate that serial BCs are warranted to document bacterial clearance.

Risk of Cardiovascular Implantable Electronic Device Infection in Patients Presenting With Gram-Negative Bacteremia.

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.

Incidence of Monomicrobial Staphylococcus aureus Bacteremia: A Population-Based Study in Olmsted County, Minnesota-2006 to 2020.

Background: Population-based studies of Staphylococcus aureus bacteremia (SAB) in the United States are limited. We provide a contemporary evaluation of SAB incidence in Olmsted County, Minnesota, from 2006 to 2020. Methods: This was a retrospective population-based study of all adult patients with SAB residing in Olmsted County from 1 January 2006 through 31 December 2020. Initial episodes of SAB were identified using the microbiology laboratory databases at both Olmsted Medical Center and Mayo Clinic Rochester. Results: Overall, 541 incident SAB cases were identified with a median age of 66.8 (interquartile range, 54.4-78.5) years, and 60.4% were male. Among these cases, 298 (56.2%) were due to methicillin-susceptible S aureus (MSSA) and 232 (43.8%) cases of methicillin-resistant S aureus (MRSA). The overall age- and sex-adjusted SAB incidence rate (IR) was 33.9 (95% confidence interval [CI], 31.0-36.8) cases/100 000 person-years (PY). Males had a higher age-adjusted IR of 46.0 (95% CI, 41.0-51.0) cases/100 000 PY compared to females (IR, 24.4 [95% CI, 21.1-27.7] cases/100 000 PY). Age- and sex-adjusted SAB IRs due to MSSA and MRSA were 18.7 and 14.6 cases/100 000 PY, respectively, and the percentage of incident SAB cases due to MRSA fluctuated across the study period. There was no apparent temporal trend in SAB incidence over the study period (P = .093). Conclusions: Our investigation represents the only contemporary population-based study in the United States. Despite the impression that SAB incidence may have increased based on Centers for Disease Control and Prevention surveillance data, our finding of no change in SAB incidence was somewhat unanticipated.

Metagenomic shotgun sequencing of blood to identify bacteria and viruses in leukemic febrile neutropenia.

Despite diagnostic advances in microbiology, the etiology of neutropenic fever remains elusive in most cases. In this study, we evaluated the utility of a metagenomic shotgun sequencing based assay for detection of bacteria and viruses in blood samples of patients with febrile neutropenia. We prospectively enrolled 20 acute leukemia patients and obtained blood from these patients at three time points: 1) anytime from onset of neutropenia until before development of neutropenic fever, 2) within 24 hours of onset of neutropenic fever, 3) 5-7 days after onset of neutropenic fever. Blood samples underwent sample preparation, sequencing and analysis using the iDTECT® Dx Blood v1® platform (PathoQuest, Paris, France). Clinically relevant viruses or bacteria were detected in three cases each by metagenomic shotgun sequencing and blood cultures, albeit with no concordance between the two. Further optimization of sample preparation methods and sequencing platforms is needed before widespread adoption of this technology into clinical practice.

Temporal trends of device-related infection in de novo transvenous implantable cardioverter-defibrillator Medicare patients with underlying kidney disease.

BACKGROUND: Kidney disease is a risk factor for device infection in transvenous implantable cardioverter-defibrillator (TV-ICD) implants, with mechanisms that include immunodeficiency and a portal of entry for bacteria that can seed indwelling devices. OBJECTIVE: The purpose of this study was to examine the impact of both kidney disease and dialysis-dependence on the incidence of device-related infection after de novo TV-ICD implantation and how the incidence changes over time in. METHODS: Medicare 100% administrative and claims data were used to identify patients who underwent de novo TV-ICD implantation between July 1, 2016, and December 31, 2018. Baseline characteristics included underlying kidney disease (none, nondialysis, dialysis) plus device infection during follow-up. Patients were followed for TV-ICD infection up to 78 weeks after implantation. Piecewise Poisson regression was used to predict the incidence of and hazard ratios for infection over time. RESULTS: Overall, 809 of 42,200 patients (1.9%) had at least 1 device infection during mean follow-up of 66 weeks: 484 of 31,217 (1.6%) none; 202 of 9151 (2.2%) nondialysis; and 123 of 1832 (6.7%) dialysis (P <.001 via log-rank test). The incidence of infection increased during the first 8-12 weeks and declined thereafter. Hazard ratios increased over time (dialysis week 12 = 4.9/1000 patient-years; week 52 = 9.8; nondialysis week 12 = 1.4; week 52 = 2.5; all P <.05), as did the difference in cumulative incidence compared with none (dialysis week 12 = Δ11.8 and week 78 = Δ53.5; nondialysis week 12 = Δ1.4 and week 78 = Δ7.0). CONCLUSION: The incidence of infection after de novo TV-ICD implantation is higher when patients have kidney disease and is substantially higher when patients are dialysis-dependent.

A Review of Coronaviruses Associated With Kawasaki Disease: Possible Implications for Pathogenesis of the Multisystem Inflammatory Syndrome Associated With COVID-19.

Multisystem Inflammatory Syndrome in Children (MIS-C), representing a new entity in the spectrum of manifestations of COVID-19, bears symptomatic resemblance with Kawasaki Disease (KD). This review explores the possible associations between KD and the human coronaviruses and discusses the pathophysiological similarities between KD and MIS-C and proposes implications for the pathogenesis of MIS-C in COVID-19. Since 2005, when a case-control study demonstrated the association of a strain of human coronavirus with KD, several studies have provided evidence regarding the association of different strains of the human coronaviruses with KD. Thus, the emergence of the KD-like disease MIS-C in COVID-19 may not be an unprecedented phenomenon. KD and MIS-C share a range of similarities in pathophysiology and possibly even genetics. Both share features of a cytokine storm, leading to a systemic inflammatory response and oxidative stress that may cause vasculitis and precipitate multi-organ failure. Moreover, antibody-dependent enhancement, a phenomenon demonstrated in previous coronaviruses, and the possible superantigenic behavior of SARS-CoV-2, possibly may also contribute toward the pathogenesis of MIS-C. Lastly, there is some evidence of complement-mediated microvascular injury in COVID-19, as well as of endotheliitis. Genetics may also represent a possible link between MIS-C and KD, with variations in FcγRII and IL-6 genes potentially increasing susceptibility to both conditions. Early detection and treatment are essential for the management of MIS-C in COVID-19. By highlighting the potential pathophysiological mechanisms that contribute to MIS-C, our review holds important implications for diagnostics, management, and further research of this rare manifestation of COVID-19.

Clinical Significance of Staphylococcus aureus in a Single Positive Blood Culture Bottle.

Clinical significance of a single positive blood culture bottle (SPBCB) with Staphylococcus aureus is unclear. We aimed to assess the significance of an SPBCB by looking at the associated outcomes. We performed a retrospective, multicenter study of patients with an SPBCB with S aureus using data collected from both electronic health records and the clinical microbiology laboratory. Overall, 534 patients with S aureus bacteremia were identified and 118 (22.1%) had an SPBCB. Among cases with an SPBCB, 106 (89.8%) were classified as clinically significant whereas 12 (10.2%) were considered contaminated or of unclear significance. A majority (92.4%) of patients received antibiotic therapy, but patients with clinically significant bacteremia were treated with longer courses (25.9 vs 5.7 days, P < .001). Significant differences in both frequency of echocardiography (65.1% vs 84.6%, P < .001) and infective endocarditis diagnosis (3.8% vs 14.2%, P = .002) were seen in those with an SPBCB compared to those with multiple positive bottles. A longer hospital length of stay and higher 90-day, 6-month, and 1-year mortality rates were seen in patients with multiple positive blood culture bottles. An SPBCB with S aureus was common among our patients. While this syndrome has a more favorable prognosis as compared to those with multiple positive blood cultures, clinicians should remain concerned as it portends a risk of infective endocarditis and mortality.

Native Vertebral Osteomyelitis in Patients with Staphylococcus Aureus Bacteremia.

BACKGROUND: The purpose of the study was to assess the epidemiology, risk factors and outcomes of native vertebral osteomyelitis (NVO) in patients with Staphylococcus aureus bacteremia (SAB). METHODS: A retrospective institutional review was conducted at Mayo Clinic, Minnesota. Patients aged ≥18 years with SAB who developed NVO from January 1, 2006 to December 31, 2020 were included and 3-month follow-up data were abstracted. Data pertaining to patient demographics, risk factors and outcomes were recorded using REDCap. A 1:2 nested case-control analysis was performed, and controls were matched according to age, sex and year of SAB diagnosis. RESULTS: A total of 103 patients had NVO. A majority (60.2%) of patients was male, with a median age of 62.0 years. Thirty-one (30.1%) cases were caused by methicillin-resistant S. aureus (MRSA). The lumbar spine was most commonly (57.6%) and the most commonly reported comorbid conditions included diabetes mellitus (36.9%) and coronary artery disease (27.2%). Mortality at three-month follow-up was 18.6%. Nested case-control analysis revealed that injection drug use (IDU) and tobacco consumption were significant risk factors associated with NVO, while chronic hemodialysis and chronic liver disease (CLD) were associated with a decreased risk of NVO. CONCLUSIONS: Atherosclerotic vascular disease was prominent in our contemporary cohort with NVO in the setting of SAB. Diabetes mellitus, tobacco consumption, older age and male sex likely contributed to this profile. Because IDU was associated with NVO, an increased number of cases should be anticipated among patients with IDU given the ongoing opioid epidemic in the United States.

Evaluation of European Heart Rhythm Association consensus in patients with cardiovascular implantable electronic devices and Staphylococcus aureus bacteremia.

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.

Diagnosis, management, and outcomes of brain abscess due to gram-negative versus gram-positive bacteria.

OBJECTIVES: Differences in management and outcomes of brain abscesses due to gram-positive (GPB) versus gram-negative bacteria (GNB) are not well defined. METHODS: A retrospective review of adult patients with brain abscesses due to monomicrobial infection from 2009 through 2020 was performed. RESULTS: A total 177 patients had a monomicrobial brain abscess; 143 (80.8%) caused by GPB and 34 (19.2%) by GNB. Patients with GNB had more history of head/neck surgery than those with GPB (58.8% vs 36.4%; P = 0.02). Pathogens in the GNB group included Pseudomonas aeruginosa (29.4%), Klebsiella spp (20.6%), and Enterobacter spp (20.6%). Pathogens in the GPB group included Staphylococcus aureus (32.2%) and Streptococcus spp (31.5%). Most patients had combined medical/surgical management (64.7% GNB vs 63.6% GPB). The median duration of antibiotic therapy was 42 days, and there was no significant difference in infection relapse or 3-month survival rate. Patients with GNB were more likely to have therapeutic failure than those with GPB (44.1% vs 22.4%; P = 0.01). CONCLUSIONS: Compared with brain abscesses caused by GPB, those due to GNB were more likely to occur in patients who had undergone prior head and neck surgery . No statistically significant difference in outcomes was observed between the groups; however, patients with GNB had a higher therapeutic failure rate than those with GPB.

Escalating incidence of infective endocarditis in Europe in the 21st century.

AIM: To provide a contemporary analysis of incidence trends of infective endocarditis (IE) with its changing epidemiology over the past two decades in Europe. METHODS: A systematic review was conducted at the Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus and Web of Science were searched for studies published between 1 January 2000 and 30 November 2020. All studies were independently reviewed by four referees and those that included a population-based incidence of IE in patients, irrespective of age, in Europe were included. Least squares regression was used to estimate pooled temporal trends in IE incidence. RESULTS: Of 9138 articles screened, 18 studies were included in the review. Elderly men predominated in all studies. IE incidence increased 4.1% per year (95% CI 1.8% to 6.4%) in the pooled regression analysis of eight studies that included comprehensive and consistent trends data. When trends data were weighted according to population size of individual countries, an increase in yearly incidence of 0.27 cases per 100 000 people was observed. Staphylococci and streptococci were the most common pathogens identified. The rate of surgical intervention ranged from 10.2% to 60.0%, and the rate of inpatient mortality ranged from 14.3% to 17.5%. In six studies that examined the rate of injection drug use, five of them reported a rate of less than 10%. CONCLUSION: Based on findings from our systematic review, IE incidence in Europe has doubled over the past two decades in Europe. Multiple factors are likely responsible for this striking increase. TRIAL REGISTERATION NUMBER: CRD42020191196.

Bloodstream infections in patients with transcatheter aortic valve replacement.

OBJECTIVE: To evaluate incidence and risk factors of bloodstream infections (BSI) in patients with transcatheter aortic valve replacement (TAVR). METHODS: We conducted a population-based study in southeastern Minnesota using the expanded Rochester Epidemiology Project (e-REP) for all adult (≥18 years) patients who underwent TAVR from January 1, 2010 to December 31, 2018. RESULTS: The incidence of BSI following TAVR was 1300 episodes/100,000 persons per annum. The median time to BSI following TAVR was 610 days and 84% were community-acquired. Forty percent of BSI cases developed infective endocarditis. Viridans group streptococci (VGS) were the most common pathogens and 80% of patients with VGS BSI had IE. CONCLUSIONS: The high incidence of BSI among TAVR patients is alarming and is likely due to advanced age and comorbid conditions. Because 40% of BSI patients also developed IE, further investigation of modifiable risk factors associated with BSI is warranted.