Optimal Timing for Cardiac Surgery in Infective Endocarditis with Neurological Complications: A Narrative Review

In patients with infective endocarditis and neurological complications, the optimal timing for cardiac surgery is unclear due to the varied risk of clinical deterioration when early surgery is performed. The aim of this review is to summarize the best evidence on the optimal timing for cardiac surgery in the presence of each type of neurological complication. An English literature search was carried out from June 2018 through July 2022. The resulting selection, comprising observational studies, clinical trials, systematic reviews and society guidelines, was organized into four sections according to the four groups of neurological complications: ischemic, hemorrhagic, infectious, and asymptomatic complications. Cardiac surgery could be performed without delay in cases of ischemic vascular neurological complication (provided the absence of severe damage, which can be avoided with the performance of mechanical thrombectomy in cases of major stroke), as well as infectious or asymptomatic complications. In the presence of intracranial hemorrhage, a delay of four weeks is recommended for most cases, although recent studies have suggested that performing cardiac surgery within four weeks could be a suitable option for selected cases. The findings of this review are mostly in line with the recommendations of the current European and American infective endocarditis guidelines

Outcome of Enterococcus faecalis infective endocardits according to the length of antibiotic therapy: Prelininary data from a cohort of 78 patients.

Background International guidelines recommend 4 weeks of treatment with ampicillin plus gentamicin (A+G) for uncomplicated native valve Enterococcus faecalis infective endocarditis (EFIE) and 6 weeks in the remaining cases. Ampicillin plus ceftriaxone (A+C) is always recommended for at least 6w, with no available studies assessing its suitability for 4w. We aimed to investigate differences in the outcome of EFIE according to the duration (4 versus 6 weeks) of antibiotic treatment (A+G or A+C). Methods Retrospective analysis from a prospectively collected cohort of 78 EFIE patients treated with either A+G or A+C. Results 32 cases (41%) were treated with A+G (9 for 4w, 28%) and 46 (59%) with A+C (14 for 4w, 30%). No significant differences were found in 1-year mortality according to the type of treatment (31% and 24% in A+G and A+C, respectively; P = 0.646) or duration (26% and 27% at 4 and 6w, respectively; P = 0.863). Relapses were more frequent among survivors treated for 4w than in those treated for 6w (3/18 [17%] at 4w and 1/41 [2%] at 6w; P = 0.045). Three out of 4 (75%) relapses occurred in cirrhotic patients. Conclusions A 4-week course of antibiotic treatment might not be suitable neither for A+G nor A+C for treating uncomplicated native valve EFIE

HACEK infective endocarditis: epidemiology, clinical features outcome: A case-control study

OBJECTIVES: The study aimed to describe the epidemiology, microbiological and clinical features of a population sample of 17 patients with HACEK-IE and to compare them with matched control patients with IE caused by Viridans group Streptococci (VGS-IE). METHODS: Description of definite (14; 82.2%) and possible (3; 17.6%) HACEK-IE included in the 'Infective Endocarditis Hospital Clínic of Barcelona' (IE-HCB) database between 1979 and 2016. Furthermore, a retrospective case-control analysis was performed, matching each case to three VGS-IE controls registered in the same database during the same period of time. RESULTS: Seventeen out of 1,209 IE cases (1.3%, 95%CI 0.69-1.91) were due to HACEK group. The most frequent isolated HACEK species were Aggregatibacter spp (11; 64.7%). Intracardiac vegetations were present in 70.6% of cases. Left heart failure (LHF) was present in 29.4% of cases. Ten patients (58.8%) required in-hospital surgery and none died during hospitalization. In the case-control analysis, there was a trend toward larger vegetations in the HACEK-IE group (median (IRQ) size=11.5 (10.0-20.0) mm vs 9.0 (7.0-13.0) mm; p=0.068). Clinical manifestations, echocardiographic findings, LHF rate, systemic emboli and other complications were all comparable (p >0.05). In-hospital surgery and mortality were similar for both groups. One-year mortality was lower for HACEK-IE (1/17 vs. to 6/48, p=0.006). CONCLUSIONS: HACEK-IE represented 1.3% of all IE cases. Clinical features and outcome were comparable with the VGS-IE control group. Despite the trend to

Emerging risk factors and the dose-response relationship between physical activity and lone atrial fibrillation: a prospective case-control study

A history of a parts per thousand yen2000 h of vigorous endurance training, tall stature, abdominal obesity, and OSA are frequently encountered as risk factors in patients with Ln-AF. Fewer than 2000 total hours of high-intensity endurance training associates with reduced Ln-AF risk

Reappraisal of [18F]FDG-PET/CT for diagnosis and management of cardiac implantable electronic device infections

Introduction and objectives: The role of [18F]FDG-PET/CT in cardiac implantable electronic device (CIED) infections requires better evaluation, especially in the diagnosis of systemic infections. We aimed to determine the following: a) the diagnostic accuracy of [18F]FDG-PET/CT in each CIED topographical region, b) the added value of [18F]FDG-PET/CT over transesophageal echocardiography (TEE) in diagnosing systemic infections, c) spleen and bone marrow uptake in differentiating isolated local infections from systemic infections, and d) the potential application of [18F]FDG-PET/CT in follow-up. Methods: Retrospective single-center study including 54 cases and 54 controls from 2014 to 2021. The Primary endpoint was the diagnostic yield of [18F]FDG-PET/CT in each topographical CIED region. Secondary analyses described the performance of [18F]FDG-PET/CT compared with that of TEE in systemic infections, bone marrow and spleen uptake in systemic and isolated local infections, and the potential application of [18F]FDG-PET/CT in guiding cessation of chronic antibiotic suppression when completed device removal is not performed. Results: We analyzed 13 (24%) isolated local infections and 41 (76%) systemic infections. Overall, the specificity of [18F]FDG-PET/CT was 100% and sensitivity 85% (79% pocket, 57% subcutaneous lead, 22% endovascular lead, 10% intracardiac lead). When combined with TEE, [18F]FDG-PET/CT increased definite diagnosis o fsystemic infections from 34% to 56% (P=.04). Systemic infections with bacteremia showed higher spleen (P=.05) and bone marrow metabolism (P=.04) than local infections. Thirteen patients without complete device removal underwent a follow-up [18F]FDG-PET/CT, with no relapses after discontinuation of chronic antibiotic suppression in 6 cases with negative follow-up [18F]FDG-PET/CT. Conclusions: The sensitivity of [18F]FDG-PET/CT for evaluating CIED infections was high in local infections but much lower in systemic infections. However, accuracy increased when [18F]FDG-PET/CT was combined with TEE in endovascular lead bacteremic infection. Spleen and bone marrow hypermetabolism could differentiate bacteremic systemic infection from local infection. Although further prospective studies are needed, follow-up [18F]FDG-PET/CT could play a potential role in the management of chronic antibiotic suppression therapy when complete device removal is unachievable

Relationship among Streptococcus gallolyticus Subsp. gallolyticus, Enterococcus faecalis and Colorectal Neoplasms in Recurrent Endocarditis: A Historical Case Series.

Objectives: The role of colorectal neoplasms (CRN) as a common potential source of recurrent Streptococcus gallolyticus subsp. gallolyticus (SGG) and Enterococcus faecalis (EF) endocarditis remains unstudied. We aimed to investigate what proportion of episodes of recurrent endocarditis are caused by a succession of SGG and EF, or vice versa, and to assess the role of a colonic source in such recurrent episodes. Methods: we conducted a retrospective analysis of two prospective endocarditis cohorts (1979-2019) from two Spanish hospitals, providing descriptive analyses of the major features of the endocarditis episodes, colonoscopy findings, and histologic results. Results: among 1552 IE episodes, 204 (13.1%) were caused by EF and 197 (12.7%) by SGG, respectively. There were 155 episodes (10%) of recurrent IE, 20 of which (12.9%) were due to a succession of SGG/EF IE in 10 patients (the first episode caused by SGG in eight cases, and by EF in two cases). The median follow-up was 86 (interquartile range 34-156) months. In 8/10 initial episodes, the causative microorganism was SGG, and all patients were diagnosed with CRN either during the initial episode or during follow-up. During the second episode of IE or follow-up, colonoscopies revealed CRN in six patients. Conclusions: There seems to be an association between SGG and EF in recurrent endocarditis that warrants further investigation. Our findings reinforce the need for systematically performing colonoscopy in the event of endocarditis caused by both microorganisms

Fosfomycin plus Beta-lactams: Synergistic Bactericidal Combinations in Methicillin-resistant (MRSA) and Glycopeptide-Intermediate Resistant (GISA) Staphylococcus aureus Experimental Endocarditis

The urgent need of effective therapies for methicillin-resistant Staphylococcus aureus (MRSA) infective endocarditis (IE) is a cause of concern. We aimed to ascertain the in vitro and in vivo activity of the older antibiotic fosfomycin combined with different beta-lactams against MRSA and glycopeptide-intermediate-resistant S. aureus (GISA) strains. Time-kill tests with 10 isolates showed that fosfomycin plus imipenem (FOF+IPM) was the most active evaluated combination. In an aortic valve IE model with two strains (MRSA-277H and GISA-ATCC 700788), the following intravenous regimens were compared: fosfomycin (2 g every 8 h [q8h]) plus imipenem (1 g q6h) or ceftriaxone (2 g q12h) (FOF+CRO) and vancomycin at a standard dose (VAN-SD) (1 g q12h) and a high dose (VAN-HD) (1 g q6h). Whereas a significant reduction of MRSA-227H load in the vegetations (veg) was observed with FOF+IPM compared with VAN-SD (0 [interquartile range [IQR], 0 to 1] versus 2 [IQR, 0 to 5.1] log CFU/g veg; P = 0.01), no statistical differences were found with VAN-HD. In addition, FOF+IPM sterilized more vegetations than VAN-SD (11/15 [73%] versus 5/16 [31%]; P = 0.02). The GISA-ATCC 700788 load in the vegetations was significantly lower after FOF+IPM or FOF+CRO treatment than with VAN-SD (2 [IQR, 0 to 2] and 0 [IQR, 0 to 2] versus 6.5 [IQR, 2 to 6.9] log CFU/g veg; P < 0.01). The number of sterilized vegetations after treatment with FOF+CRO was higher than after treatment with VAN-SD or VAN-HD (8/15 [53%] versus 4/20 [20%] or 4/20 [20%]; P = 0.03). To assess the effect of FOF+IPM on penicillin binding protein (PBP) synthesis, molecular studies were performed, with results showing that FOF+IPM treatment significantly decreased PBP1, PBP2 (but not PBP2a), and PBP3 synthesis. These results allow clinicians to consider the use of FOF+IPM or FOF+CRO to treat MRSA or GISA IE.Copyright © 2015, American Society for Microbiology. All Rights Reserved

Diagnostic accuracy of 18F-FDG PET/CT in infective endocarditis and implantable cardiac electronic device infection: A cross-sectional study.

Early diagnosis of infective endocarditis (IE) is based on the yielding of blood cultures and echocardiographic findings. However, they have limitations and sometimes the diagnosis is inconclusive, particularly in patients with prosthetic valves (PV) and implantable cardiac electronic devices (ICED). The primary aim of this study was to evaluate the diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with suspected IE an ICED infection. METHODS: A prospective study with 80 consecutive patients with suspected IE and ICED infection (65 men and 15 women with a mean age of 68±13 years old) between June 2013 and May 2015 was performed in our hospital. The inclusion criteria was clinically suspected IE and ICED infection at the following locations: native valve (NV) (n = 21), PV (n = 29) or ICED (n = 30) [(automatic implantable defibrillator (n = 11) or pacemaker (n = 19)]. Whole-body 18F-FDG PET/CT with a myocardial uptake suppression protocol with unfractionated heparin was performed in all patients. The final diagnosis of infection was established by the IE study Group according to the clinical, echocardiographic and microbiological findings. RESULTS: A final diagnosis of infection was confirmed in 31 patients: NV (n = 6), PV (n = 12) and ICED (n = 13). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for 18F-FDG PET/CT was 82%, 96%, 94% and 87%, respectively. 18F-FDG PET/CT was false negative in all cases with infected NV. 18F-FDG PET/CT was able to reclassify 63/70 (90%) patients initially classified as possible IE by modified Duke criteria. In 18/70 cases 18F-FDG PET/CT changed possible to definite IE (26%) and in 45/70 cases changed possible to rejected IE (64%). Additionally, 18F-FDG PET/CT identified 8 cases of septic embolism and 3 colorectal cancer in patients with final diagnosis of IE. CONCLUSION: 18F-FDG PET/CT proved to be a useful diagnostic tool in suspected IE and ICED infection and should be included in the diagnostic algorithm for early diagnosis. 18F-FDG PET/CT is not useful in the diagnosis of IE in NV, but should be also considered in the initial assessment of this complex scenario to rule out extracardiac complications and possible neoplasms

Effectiveness of vancomycin plus cloxacillin compared with vancomycin, cloxacillin and daptomycin single therapies in the treatment of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in a rabbit model of experimental endocarditis

Objectives: To investigate if the addition of cloxacillin to vancomycin enhances the activity of both monotherapies for treating MSSA and MRSA experimental endocarditis (EE) in rabbits. Methods: Vancomycin plus cloxacillin was compared with the respective monotherapies and daptomycin. In vitro time-kill studies were performed using standard (105 cfu) and high (108 cfu) inocula of five MRSA, one glycopeptide-intermediate (GISA) and five MSSA strains. One MSSA (MSSA-678) and one MRSA (MRSA-277) strain were selected to be used in the in vivo model. A human-like pharmacokinetics model was applied and the equivalents of cloxacillin 2 g/4 h IV and daptomycin 6 mg/kg/day IV were administered. To optimize vancomycin activity, dosage was adjusted to achieve an AUC/MIC ≥400. Results: Daptomycin sterilized significantly more vegetations than cloxacillin (13/13, 100% versus 9/15, 60%; P = 0.02) and showed a trend of better activity than vancomycin (10/14, 71%; P = 0.09) and vancomycin plus cloxacillin (10/14, 71%; P = 0.09) against MSSA-678. Addition of cloxacillin to vancomycin (13/15, 87%) was significantly more effective than vancomycin (8/16, 50%; P = 0.05) and showed similar activity to daptomycin (13/18, 72%; P = 0.6) against MRSA-277. In all treatment arms, the bacterial isolates recovered from vegetations were re-tested and showed the same daptomycin susceptibility as the original strains. Conclusions: Vancomycin plus cloxacillin proved synergistic and bactericidal activity against MRSA. Daptomycin was the most efficacious option against MSSA and similar to vancomycin plus cloxacillin against MRSA. In settings with high MRSA prevalence, vancomycin plus cloxacillin might be a good alternative for empirical therapy of S. aureus IE

The Combination of Daptomycin plus Fosfomycin has Synergistic, Potent and Rapid Bactericidal Activity against Methicillin-ResistantStaphylococcus aureus(MRSA) in a Rabbit Model of Experimental Endocarditis (EE).

This study aims to investigate whether the addition of fosfomycin or cloxacillin to daptomycin provides better outcomes in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) experimental aortic endocarditis in rabbits. Five MRSA strains were used to perform in vitro time-kill studies at standard (105) and high (108) inocula. Combined therapy was compared with daptomycin monotherapy treatment in the MRSA experimental endocarditis model. A human-like pharmacokinetics model was applied and the equivalents of cloxacillin 2g/4hiv, fosfomycin 2g/6h iv and daptomycin 6-10mg/kg/d iv were administered. The combination of daptomycin and fosfomycin or cloxacillin was synergistic in the five strains tested at both inocula. A bactericidal effect was detected in four out of five strains tested with both combinations. The MRSA-277 strain (vancomycin MIC, 2 mcg/mL) was used for the experimental endocarditis model. Daptomycin plus fosfomycin significantly improved the efficacy of daptomycin monotherapy at 6 mg/kg/d in terms of both the proportion of sterile vegetations (100% vs. 72%, P=.046) and the decrease in the density of bacteria within the vegetations (P=.025). Daptomycin plus fosfomycin was as effective as daptomycin monotherapy at 10 mg/kg/d (100% vs. 93%, P=1.00) and had similar activity to daptomycin plus cloxacillin when daptomycin was administered at 6 mg/kg/d (100% vs. 88%, P=0.48). Daptomycin non-susceptibility was not detected in any of the isolates recovered from vegetations. In conclusion, for the treatment of MRSA experimental endocarditis, the combination of daptomycin plus fosfomycin showed synergistic and bactericidal activity.Copyright © 2018 American Society for Microbiology