Miró, José M.

Abstract Background The 2023 Duke-ISCVID criteria for IE were recently introduced to improve classification of IE for research and clinical purposes (Table 1). We compared the diagnostic accuracy of the new criteria with the 2000 modified Duke criteria, the 2015 European Society of Cardiology (ESC) criteria and a clinically adjudicated reference standard by a panel of international experts on IE.Table 1:Overview of changes in criteria from 2000 modified Duke to 2023 Duke-ISCVIDAdapted from: Fowler et al, Clinical Infectious Diseases, 2023 Methods The study population consisted of consecutively enrolled patients suspected to have IE and discussed by the IE team of the Amsterdam University Medical Center (AMC) between October 2016 and March 2021. A panel of international experts on IE assigned a final diagnosis, which served as the reference standard. We compared the definite classification of the 2023 Duke-ISCVID criteria against this reference standard. We also evaluated accuracy of the new criteria, excluding data obtained from cardiac surgery and pathology (“Clinical Criteria”). Lastly, we quantified the added value of the proposed changes to the criteria, and compared the 2023 Duke-ISCVID to previous criteria using the McNemar test. We performed sensitivity analyses in patients who underwent cardiac surgery and patients who underwent TEE. Results 595 patients with suspected IE were included, of whom 399 (67%) were adjudicated as having IE. 111 patients (19%) had prosthetic valve IE, 48 (8%) had cardiac implantable electronic device IE. The 2023 Duke-ISCVID criteria were more sensitive than the modified Duke or ESC criteria (84.2 vs 74.9 vs 80%,respectively, p < 0.001 for ISCVID vs ESC criteria) without significant loss of specificity (Table 2). After excluding cardiac surgery/pathology results, the 2023 Duke-ISCVID Clinical Criteria also had significantly better sensitivity than the modified Duke and ESC criteria, again without losing specificity. The changes in the 'major microbiological' and 'imaging' criteria had the most impact (Figure 1). Findings were robust in sensitivity analyses (Table 3). When classifying ‘definite’ and ‘possible’ IE as a positive test, the 2023 Duke-ISCVID criteria had 99% sensitivity compared to the reference standard, but specificity decreased to 21%.Table 2:Diagnostic accuracy of modified Duke, ESC and Duke-ISCVID criteria Sensitivity and specificity are against the reference standard (adjudication panel). The Clinical Criteria classification is the Duke-ISCVID classification when results from surgery or post-mortem studies are not used to determine classification.Table 3:Sensitivity analyses of accuracy of Duke-ISCVID criteria In the Definite + Possible analysis, patients with possible IE according to the Duke-ISCVID criteria were also considered as having IE. All comparisons are against the reference standard (adjudication panel). Conclusion In this cohort, the 2023 Duke-ISCVID criteria represent a significant advance in the diagnostic classification of patients suspected of IE. Added value of new Duke-ISCVID criteria compared to modified Duke criteria Each point (red square for sensitivity, blue circle for specificity) provides the diagnostic accuracy measure for the 2000 modified Duke Criteria with addition of a specific change from the Duke-ISCVID criteria. The horizontal bars represent the 95% confidence interval for the point estimate. The top points represent the modified Duke criteria without addition, the bottom points are the complete Duke-ISCVID criteria. Disclosures Larry M. Baddour, MD, Boston Scientific: Advisor/Consultant|Roivant Sciences: Advisor/Consultant Arnold S. Bayer, MD, Akagera Medicines: Grant/Research Support|ContraFect Corporation: Grant/Research Support Emanuele Durante Mangoni, MD,, PhD, Advanz pharma: Advisor/Consultant|Advanz pharma: Grant/Research Support|Advanz pharma: Honoraria|Angelini: Grant/Research Support|Angelini: Honoraria|Genentech: Advisor/Consultant|Genentech: Board Member|Genentech: Honoraria|Infectopharm: Grant/Research Support|Menarini: Board Member|Menarini: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Board Member|Pfizer: Grant/Research Support|Pfizer: Honoraria|Roche: Advisor/Consultant|Roche: Board Member|Roche: Honoraria Thomas L. Holland, MD, Aridis: Advisor/Consultant|Basilea Pharmaceutica: Advisor/Consultant|Karius: Advisor/Consultant|Lysovant: Advisor/Consultant Adolf W. Karchmer, MD, Karius: Grant/Research Support|Up To Date: Honoraria Vance G. Fowler, MD, MHS, Amphliphi Biosciences, Integrated Biotherapeutics; C3J, Armata, Valanbio; Akagera, Aridis, Roche, Astra Zeneca: Advisor/Consultant|Genentech, Regeneron, Deep Blue, Basilea, Janssen;: Grant/Research Support|Infectious Diseases Society of America: Honoraria|MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck; Medical Biosurfaces; Locus; Affinergy; Contrafect; Karius;: Grant/Research Support|Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny,: Advisor/Consultant|Sepsis diagnostic: Patent pending|UpToDate: Royalties|Valanbio and ArcBio: Stock Options

Abstract Background Cardiac implantable electronic device-related infective endocarditis (CIED-IE) comprises 10–57% of total CIED infections. Patients with definite CIED-IE who fulfill both major modified Duke criteria have not been well characterized. Methods Data from the Multicenter Electrophysiologic Device Infection Cohort, a prospective, multinational study of CIED infections were used to describe a subset of patients with CIED-IE who met both major Duke criteria for definite IE (bloodstream infection and intracardiac vegetations [VEG]). Results Of 433 patients with CIED infection, 144 (33.3%) had definite CIED-IE. The median age was 68 years and 77.1% were male. Twelve (8.3%) had past CIED infection. Seventy-seven patients (53.5%) had permanent pacemakers, 38 (26.4%) had implantable cardioverter defibrillators, and 29 (20.1%) had combination devices. The median time following the last device procedure was 550 days. CIED-IE was early in 60 patients (41.7%) and late in 84 (58.3%). Most patients presented with fever (77.8%) and sepsis (44.4%) with a median symptom duration of 7 days. On echocardiography, lead VEG was noted in 125 patients (86.8%) and valvular VEG in 54 patients (37.5%) with the tricuspid valve involved in 56.5%. On the basis of VEG location, there were 90 patients (62.5%) with isolated lead-associated IE (LAE), 19 patients (13.2%) with isolated valve-associated IE (VAE), and 35 patients (24.3%) with both (LVAE). All patients had positive blood cultures and 63/119 (52.9%) had positive lead cultures. The predominant organism in blood was Staphylococcus aureus (42.4%), followed by coagulase-negative staphylococci (20.1%). CIED removal occurred in 131 patients (91%). There were 25 deaths during the index hospitalization and 34 total deaths (24.3%) by 6 months. Mortality correlated with age >75 (P = 0.023) and sepsis on presentation (P = 0.052). Infecting organism, site of VEG, and device removal did not impact the risk of death. Conclusion Definite CIED-IE is relatively common. The majority of patients tend to have late-onset infection and often present with sepsis. S. aureus is the dominant organism causing definite CIED-IE. Isolated LAE occurs in 63% of patients. Older age and sepsis on admission are associated with higher mortality. Disclosures All authors: No reported disclosures.

The efficacy of azithromycin or clarithromycin was compared to that of amoxicillin, clindamycin, or erythromycin for the prevention of viridans group streptococcus experimental endocarditis. Rabbits with catheter-induced aortic valve vegetations were given no antibiotics or two doses of amoxicillin at 25 mg/kg of body weight, azithromycin at 10 mg/kg, clarithromycin at 10 mg/kg, clindamycin at 40 mg/kg followed by clindamycin at 20 mg/kg, or erythromycin at 10 mg/kg. Antibiotics were administered 0.5 h before and 5.5 h after intravenous infusion of 5 x 10(5) CFU of Streptococcus milleri. Forty-eight hours after bacterial inoculation, the rabbits were killed and aortic valve vegetations were aseptically removed and cultured for bacteria. Infective endocarditis occurred in 88% of untreated animals, 1% of animals receiving amoxicillin, 9% of animals receiving erythromycin, 0% of animals receiving clindamycin, 2.5% of animals receiving clarithromycin, and 1% of animals receiving azithromycin. All five regimens were more effective (P < 0.001) than no prophylaxis. Erythromycin was less effective (P < 0.05) than amoxicillin or clindamycin. Azithromycin or clarithromycin was as effective as amoxicillin, clindamycin, or erythromycin for the prevention of viridans group streptococcus experimental endocarditis in this model.

Objective To explore differences in clinical manifestations and outcomes in those patients who develop infection after undergoing initial implantation versus reoperation. Methods We compared cases of cardiac implantable electronic device (CIED) infection based on initial implantation versus reoperation from 11 centres. Results There were 432 patients with CIED infection, 178 occurring after initial device placement and 254 after repeat reoperation. No differences were seen in age, sex or device type. Those with infection after initial implant had a higher Charlson Comorbidity Score (median 3 (IQR 2–6) vs 2 (IQR 1–4), p<0.001), shorter time since last procedure (median 8.9 months (IQR 0.9–33.3) vs 19.5 months (IQR 1.1–62.9), p<0.0001) and fewer leads (2.0±0.6vs 2.5±0.9, p<0.001). Pocket infections were more likely to occur after a reoperation (70.1%vs48.9%, p<0.001) and coagulase negative staphylococci (CoNS) was the most frequently isolated organism in this group (p=0.029). In contrast, initial implant infections were more likely to present with higher white cell count (10.5±5.1 g/dL vs 9.5±5.4 g/dL, p=0.025), metastatic foci of infection (16.9%vs8.7%, p=0.016) and sepsis (30.9%vs19.3%, p=0.006). There were no differences in in-hospital (7.9%vs5.2%, p=0.31) or 6-month mortality (21.9%vs14.0%, p=0.056). Conclusions CIED infections after initial device implant occur earlier, more aggressively, and often due to Staphylococcus aureus. In contrast, CIED infections after reoperation occur later, are due to CoNS, and have more indolent manifestations with primary localisation to the pocket.