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Background: MRSA (methicillin-resistant Staphylococcus aureus)-infective endocarditis (IE) is associated with high morbidity and mortality. This study aimed to assess data from patients with MRSA-IE across multiple facilities in Japan, with a specific focus on antimicrobial therapy and prognosis., Methods: This retrospective study enrolled patients with a confirmed diagnosis of IE attributed to MRSA, spanning the period from January 2015 to April 2019., Results: Sixty-four patients from 19 centers were included, with a median age of 67 years. The overall mortality rate was 28.1% at 30 days, with an in-hospital mortality of 45.3%. The most frequently chosen initial anti-MRSA agents were glycopeptide in 67.2% of cases. Daptomycin and linezolid were selected as initial therapy in 23.4% and 17.2% of cases, respectively. Approximately 40% of all patients underwent medication changes due to difficulty in controlling infection or drug-related side effects. Significant prognostic factors by multivariable analysis were DIC for 30-day mortality and surgical treatment for 30-day and in-hospital mortality. For vancomycin as initial monotherapy, there was a trend toward a worse prognosis for 30-day and in-hospital mortality (OR, 6.29; 95%CI, 1.00-39.65; p = 0.050, OR, 3.61; 95%CI, 0.93-14.00; p = 0.064). Regarding the choice of initial antibiotic therapy, statistical analysis did not show significant differences in prognosis., Conclusion: Glycopeptide and daptomycin were the preferred antibiotics for the initial therapy of MRSA-IE. Antimicrobial regimens were changed for various reasons. Prognosis was not significantly affected by choice of antibiotic therapy (glycopeptide, daptomycin, linezolid), but further studies are needed to determine which antimicrobials are optimal as first-line agents., Competing Interests: Declaration of Competing interest Tokimatsu I. received scholarship donations from Shionogi Pharmaceuticals, Inc. and Daiichi Sankyo Co. Ltd. Ukimura A. received scholarship donations from Shionogi Pharmaceuticals, Inc. Hiroshige Mikamo received speaker honoraria from MSD K.K., FUJIFILM Toyama Chemical Co., Ltd., Miyarisan Pharmaceutical Co., Daiichi Sankyo Co., Ltd., Pfizer Japan Inc., Sanofi K.K., Sumitomo Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Shionogi & Co., Ltd. Japan, Kowa Co. Ltd., Gilead Sciences K.K., GSK Group of Companies, Saraya Co. Ltd., Tsumura & Co. Japan, Nippon Becton Dickinson Company, Ltd., and FUKOKU Co., Ltd., grant supports from Asai Kasei Pharma Co., Shionogi & Co., Ltd., Sumitomo Pharma Co., Ltd., and FUKOKU Co., Ltd. Mitsutake K, Shinya N, Seki M, Ohara T, Uemura K, Fukunaga M, Sakai J, Nagao M, Sata M, Hamada Y, Kawasuji H, Yamamoto Y, Nakamatsu M, Koizumi Y, Aoyagi T, Sawai T, Tanaka T, Izumikawa K, Takayama Y, Nakamura K, Kanemitsu K, Nakajima K, and Akine D have no conflict of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Infective endocarditis (IE) caused by MRSA (methicillin-resistant Staphylococcus aureus) is associated with a high mortality rate. This study aimed to elucidate the characteristics of patients with MRSA-IE in Japan and identify the factors associated with prognosis., Methods: This retrospective study included patients with a confirmed diagnosis of IE caused by MRSA, between January 2015 and April 2019., Results: A total of 65 patients from 19 centers were included, with a mean age of 67 years and 26 % were female. Fifty percent of the patients with IE were had nosocomial infections and 25 % had prosthetic valve involvement. The most common comorbidities were hemodialysis (20 %) and diabetes (20 %). Congestive heart failure was present in 86 % of patients (NYHA class I, II: 48 %; III, IV: 38 %). The 30-day and in-hospital mortality rates were 29 % and 46 %, respectively. Multi-organ failure was the primary cause of death, accounting for 43 % of all causes of death. Prognostic factors for in-hospital mortality were age, disseminated intravascular coagulation, daptomycin and/or linezolid as initial antibiotic therapy, and surgery. Surgical treatment was associated with a lower mortality rate (odds ratio [OR], 0.026; 95 % confidence interval [CI], 0.002-0.382; p = 0.008 for 30-day mortality and OR, 0.130; 95 % CI; 0.029-0.584; p = 0.008 for in-hospital mortality)., Conclusion: Mortality due to MRSA-IE remains high. Surgical treatment is a significant prognostic predictor of MRSA-IE., Competing Interests: Declaration of competing interest Tokimatsu I. received scholarship donations from Shionogi Pharmaceuticals, Inc. and Daiichi Sankyo Co., Ltd. Ukimura A. received scholarship donations from Shionogi Pharmaceuticals Inc. Hiroshige Mikamo received speaker honoraria from MSD K.K., FUJIFILM Toyama Chemical Co., Ltd., Miyarisan Pharmaceutical Co., Daiichi Sankyo Co., Ltd., Pfizer Japan Inc., Sanofi K.K., Sumitomo Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Shionogi & Co., Japan. Ltd., Kowa Co. Ltd., Gilead Sciences K.K., the GSK Group of Companies, Saraya Co. Ltd., and Tsumura and Co. Japan, Nippon Becton Dickinson Company, Ltd., and FUKOKU Co., Ltd., and grant support from Asai Kasei Pharma Co., Shionogi & Co., Ltd., Sumitomo Pharma Co., Ltd., and FUKOKU Co., Ltd. Mitsutake K, Shinya N, Seki M, Ohara T, Uemura K, Fukunaga M, Sakai J, Nagao M, Sata M, Hamada Y, Kawasuji H, Yamamoto Y, Nakamatsu M, Koizumi Y, Aoyagi T, Sawai T, Tanaka T, Izumikawa K, Takayama Y, Nakamura K, Kanemitsu K, Nakajima K, and Akine D have no conflict of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Infective endocarditis remains associated with substantial mortality and morbidity rates, and the presence of acute heart failure (AHF) compromises clinical results after valve surgery; however, little is known in cardiogenic shock (CGS) patients. This study evaluated the clinical results and risk of mortality in CGS patients after valve surgery., Methods and results: This study enrolled 585 patients who underwent valve surgery for active endocarditis at 14 institutions between 2009 and 2017. Of these patients, 69 (12%) were in CGS, which was defined as systolic blood pressure <80 mmHg and severe pulmonary congestion, requiring mechanical ventilation and/or mechanical circulatory support, preoperatively. The predictors of CGS were analyzed, and clinical results of patients with non-CGS AHF (n=215) were evaluated and compared.Staphylococcus aureusinfection (odds ratio [OR] 2.19; P=0.044), double valve involvement (OR 3.37; P=0.003), and larger vegetation (OR 1.05; P=0.036) were risk factors for CGS. Hospital mortality occurred in 27 (13%) non-CGS AHF patients and in 15 (22%) CGS patients (P=0.079). Overall survival at 1 and 5 years in CGS patients was 76% and 69%, respectively, and there were no significant differences in overall survival compared with non-CGS AHF patients (P=1.000)., Conclusions: Clinical results after valve surgery in CGS patients remain challenging; however, mid-term results were equivalent to those of non-CGS AHF patients.

Background: Mitral valve repair has been proved to provide better outcomes when compared with replacement in degenerative disease. However, it is still unclear that benefits of repair still remain in active endocarditis. Patient clinical conditions and severity of tissue destruction might limit successful durable repair., Methods: Of all 247 patients who received surgery during active phase of native left-sided endocarditis from Jan 2006 to Dec 2017, 114 had mitral valve procedures due to active infection of mitral valve apparatus (38 repair and 76 replacement). Perioperative data and mid-term outcomes were retrospectively compared., Results: Mean age was 46.4 years old. Repair group had significantly less patients with NYHA class IV (18.4% vs 56.6%, p = 0.001). Both groups had preserved ejection fraction but accompanied by severe pulmonary hypertension. Major organism was streptococci (50%) and timing of surgery was 11 days after diagnosis. Bypass and cross-clamp time were similar but repair group had significantly less combined procedures. Bi-leaflet involvement was common (47.4% vs 57.6%) and valve lesions were comparable. There was 13.2% of postoperative moderate to severe mitral regurgitation in repair group without recurrent endocarditis. Repair group tended to have better 5-year survival estimates (91.6% vs 70.0%, p = 0.08) with comparable reoperation rate (7.9% vs 2.6%). By logistic regression analysis, mitral valve replacement was more likely to be performed in patients with decompensated heart failure and combined procedures., Conclusions: Mitral valve repair during active endocarditis can be safely performed with good mid-term outcomes, especially in selected group of patients without extremely high surgical risk.

Background: The benefit of early surgery for IE is yet to be determined in non-Western countries. We conducted this study to evaluate the role of early surgery in infective endocarditis (IE) in Japan., Methods: IE admissions in Japan were prospectively registered using a nation-wide WEB-based registration system (CArdiac Disease REgistration, CADRE). The impact of early surgery on in-hospital mortality was assessed in native valve endocarditis (NVE) and prosthetic valve endocarditis (PVE). Risk factors for in-hospital death were assessed by multiple logistic regression analysis. The propensity score for early surgery was calculated to adjust the impact of early surgery., Results: From September 2006 to May 2009, 348 NVE and 81 PVE were registered. In NVE, early surgery was preferable in every quartile stratified with the propensity score and the summary odds ratio (OR) and 95% confidence interval (CI) was 0.12 (0.05-0.31). The predictors of in-hospital death were Staphylococcus aureus infection (OR 3.5, 95% CI 1.26-9.7), heart failure (OR 6.74, 95% CI 2.43-18.7) and early surgery (OR 0.07, 95% CI 0.03-0.2). In PVE, the predictors of in-hospital death were age (OR 1.09, 95% CI 1.01-1.18), S. aureus infection (OR 5.8, 95% CI 1.4-24.01) and heart failure (OR 7.44, 95% CI 1.81-30.67), whereas early surgery was not (OR 0.51, 95% CI 0.12-2.16)., Conclusion: Early surgery for NVE is associated with improved survival in a wide range of clinical subgroups in Japan. In PVE a survival benefit of early surgery is not clear., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background and Aim of the Study: Prosthetic valve endocarditis (PVE) is considered a time-related event. The study aim was to compare the clinical characteristics and outcomes of early- and late-onset PVE, and to investigate potential preventive measures for each condition., Methods: A total of 47 consecutive patients undergoing surgery for PVE between January 1986 and December 2011 were analyzed retrospectively, and classified as an early-onset group (n = 26; PVE occurring within 12 months after previous surgery) and late-onset group (n = 21; PVE occurring after 12 months)., Results: The prosthetic valve position significantly affected the incidence of endocarditis: 21 cases (80.7%) in the early-onset group had infected aortic prostheses, while 18 (85.7%) in the late-onset group had infected mitral prostheses (p = 0.028). PVE significantly affected bioprosthetic valves in the early-onset group (18 cases, 69.2%) and mechanical valves in the late-onset group (17 cases, 80.9%) (p < 0.01). Staphylococcus spp. infections were predominant in the early-onset group (21 cases, 80.7%), and Streptococcus spp. in the late-onset group (five cases, 23.8%) (p = 0.03). Operative deaths occurred in both the early-onset (n = 6; 23.0%) and late-onset (n = 2; 9.5%) groups (p = 0.11). The long-term mortality in the early-onset and late-onset groups, respectively, was 40.3 +/- 17.7% and 85.1 +/- 7.9% at 10 years, and 40.3 +/- 17.7% and 72.9 +/- 13.1% at 15 years (p 0.047). Freedom from recurrent endocarditis after two years in the early- and late-onset groups, respectively, was 67.8 +/- 10.1% and 88.8 +/- 7.4% (p = 0.048)., Conclusion: Clinical characteristics and outcomes differed significantly between early- and late-onset PVE. The clinical outcomes of patients with early PVE tend to be serious, and therefore stringent care should be taken to avoid contamination during the initial surgery and hence to reduce the incidence of the condition.

Background:  It is important to manage a potentially fatal disease such as infective endocarditis (IE) based on evidence and guidelines for treatment published by academic societies. To clarify the current status of IE in Japan, we conducted a nationwide survey of IE (CArdiac Disease REgistration-Infective Endocarditis [CADRE-IE])., Methods and Results:  We collected data on every aspect of IE using web-based survey. Only a Japanese Circulation Society-certified cardiologists who had managed a case of IE could register the patient when the outcome was known. There were 513 cases (320 men, 193 women) from 114 institutions. The median age was 61 years and more than 80% of the patients had underlying cardiac diseases. The majority was valvular heart disease, in which mitral regurgitation was a leading cause. Most of the patients had some predisposing factors, among which, decayed teeth or periodontitis was a leading factor. Streptococci were found in approximately 52% and staphylococci were found in 32% in positive-culture cases. Methicillin-resistant Staphylococcus aureus was found in 7.5%. Congestive heart failure was found in 43% and intracranial complications were found in 31%. Most of the patients were discharged (65%) but in-hospital death occurred in 11%., Conclusions:  IE is still a lethal disease affecting older patients. The information obtained from the survey should be very helpful for physicians.

Mitral valve repair is preferred to replacement in infective endocarditis, but in the active phase, it often requires extensive debridement of infected tissue and complex reconstruction. We investigated 22 consecutive native mitral valve operations during active-phase infective endocarditis. The time from initiation of medical treatment to operation was 16.8 ± 16.4 days. Mitral valve repair was performed in 15 (68.2%) patients, using prosthetic annuloplasty in 14, an autologous pericardial patch in 11, and artificial chordal replacement in 9. Hospital mortality was 9.1% (2 patients), due to subarachnoid hemorrhage and pneumonia. One patient died 26 months after valve replacement due to congestive heart failure. The postoperative left ventricular end-diastolic dimension was significantly smaller (45.7 ± 5.6 vs. 53.3 ± 10.2 mm) and ejection fraction was significantly higher (57.0% ± 14.7% vs. 40.1% ± 8.2%) in patients who underwent valve repair compared to those who had valve replacement. Mitral regurgitation requiring reoperation occurred in 3 patients during follow-up. Mitral valve repair is feasible in active-phase infective endocarditis, and results in improved regression of left ventricular dimensions compared to valve replacement. However, complex mitral valve repair with extensive leaflet resection may not have long-term durability.

In-hospital and long-term mortality of infective endocarditis (IE) are well noted, but the studies for mid-term (90-day) mortality of IE is still limited. We determine the mid-term mortality rate of IE and its significant predictors. Seventy patients with IE were hospitalised at St. Luke's International Hospital between January 1996 and March 2009, of whom 62 consecutive patients could be followed up for 90 days after diagnosis. We then calculated Kaplan-Meier (KM) estimates and performed time-to-event analysis. The mean (standard deviation, SD) age was 66.6 (15.3) years. Thirty-five patients (56%) were male. Blood cultures were positive in 87%. Causative microorganisms were: viridans group streptococci (23%), β-streptococci (16%), Staphylococcus aureus (15%), including methicillin-resistant S. aureus (MRSA) (5%). Thirty-three cases (53%) had at least one complication such as heart failure (34%), central nervous system (CNS) complication (29%) or emboli peripheral to CNS (6%). KM estimates (95% CI) of the 90-day mortality was 14.5% (7.8-25%). In multiple regression analysis using the Cox proportional hazards model, hazard ratios of at least one complication for the 90-day mortality was 8.2 (1.4-155). Mid-term mortality of IE continues to be high and the presence of at least one complication may be considered as an independent risk factor of mid-term mortality.

Background: This study was performed to identify risk factors for hospital death in patients with acute and active infective endocarditis (AAIE) after surgical intervention., Methods and Results: From 1980 to 2004, 94 patients underwent surgery for AAIE (age range, 3-77 years; 76% males). Congestive heart failure (CHF) was present in 44 patients, as well as vegetations in 64, septicemia in 16, abscesses in 17, and emboli in 22; 16 patients had prosthetic valve endocarditis. Streptococci were the most common bacteria (34 patients), followed by staphylococci (17 patients). Mechanical valves were selected for 73 patients and bioprosthetic valves for 16. Mitral valve plasty was performed in 4 patients. Aortic root or aorto-mitral discontinuity was repaired in 17 patients, including Manouguian's double valve replacement in 6 and aortic root replacement in 4. Overall hospital mortality was 15% (14 patients). Univariate analysis identified CHF (p=0.016), abscess (p=0.014), and prosthetic valve endocarditis (p=0.043) as risk factors. However, multivariate analysis only identified CHF (p=0.019) as an independent risk factor., Conclusion: In AAIE, early surgical intervention is advisable before the occurrence of complications such as root abscess and CHF, particularly before the onset of CHF.

Despite developments in preventative and medical therapy, infective endocarditis (IE) carries a high rate of mortality. Risk factors for mortality are unknown in pediatric and adult patients with congenital heart disease (CHD). We determined the risk factors for in-hospital mortality in pediatric and adult patients with CHD. A retrospective observational cohort study was conducted from January 1997 to December 2001 in Japan. Of the 239 patients for whom complete data were available, 216 patients with CHD were identified. Outcomes were alive or deceased. The proposed modified Duke's criteria identified 137 patients, aged 1 month to 62 years with a median of 12 years, with IE. In-hospital mortality was 10%. Four risk factors were independently associated with mortality by stepwise logistic regression analysis: (1) vegetation size > or =20 mm (odds ratio 40.6, 95% confidence interval 2.42 to 681); (2) age <1 year (odds ratio 19.5, 95% confidence interval 1.74 to 219); (3) presence of heart failure (odds ratio 7.16, 95% confidence ratio 1.34 to 38.4); and (4) Staphylococcus aureus as a causative organism (odds ratio 5.68, 95% confidence interval 1.16 to 27.9). Surgical intervention emerged as a predictive factor for lower in-hospital mortality (odds ratio 0.045, 95% confidence interval 0.003 to 0.70) by stepwise logistic regression analysis. In conclusion, surgical intervention, which decreases the risk of in-hospital mortality, should always be considered.

Objectives: To evaluate the changes in the clinical background to infective endocarditis and identify the contributing factors to in-hospital deaths over the last 20 years., Methods: Seventy-five patients (mean age 48.2 +/- 24.0 years) with infective endocarditis treated between January 1984 and December 2003 at our hospital were evaluated retrospectively. The patients were divided into two groups (first decade, n = 26 and second decade, n = 49)., Results: The infection route was unknown in 65% of the patients, but the oral route was the most common known route (16.0%). Congenital heart disease (24.0%)was the most common background disease, followed by valvular heart disease (22.7%), and post prosthetic valve replacement (22.7%). The mitral valve was most frequently infected(56.0%), followed by the aortic valve (34.7%). Multi-valve infection was present in 13.3% of the patients. Although the frequency of streptococcal endocarditis reduced, that of staphylococcal endocarditis increased in the second decade. The overall in-hospital mortality was 26.7%, but slightly improved in the second decade (34.6% vs 22.4%, p = 0.26). The overall in-hospital mortality was similar between the surgically treated group and the non-surgically treated group (25.0% vs 27.3%, NS). In the surgically treated group, in-hospital mortality was lower in the second decade than the first decade, but higher in the group treated for active infective endocarditis. Multivariate analysis found age > or = 51 years, renal insufficiency, neurological abnormality, and culture negative as predictors of in-hospital mortality., Conclusions: Rapid and appropriate primary medical treatment are important in the active phase of infective endocarditis. Age > or = 51 years was the strongest predictor of in-hospital infective endocarditis death.