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Objectives: Clinical experience in the use of teicoplanin for treating enterococcal infective endocarditis (EIE) is scarce. The aim of this study was to describe the characteristics and outcomes of patients with EIE treated with teicoplanin monotherapy compared to standard therapy with ampicillin plus ceftriaxone., Methods: All consecutive adult patients diagnosed with EIE between January 2018 and September 2022 at a referral centre were reviewed. Characteristics of individuals treated with teicoplanin for ≥14 days [the treated with teicoplanin (TT) group] were compared with those who received ampicillin plus ceftriaxone (AC group)., Results: Sixty-six patients were included [61 (92%) E. faecalis infective endocarditis (IE) and 5 (8%) E. faecium IE]. Twenty-seven (41%) received teicoplanin: eight as first-line treatment and 19 as continuation therapy.The median duration of teicoplanin treatment was 30 (25-43) days. Surgery was indicated in 14/27 (52%) in the TT group and in 21/39 (54%) in the AC group, but was finally performed in 11/14 (79%) and 13/21 (62%) (P = 0.46), respectively. In-hospital mortality rate was 3/27 (11%) in the TT group and 12/39 (31%) in the AC group (P = 0.06). Patients treated with teicoplanin were more often discharged on outpatient parenteral antibiotic therapy [18/27 (67%) versus 6/39 (15%), P < 0.001] and median hospital stay was shorter [29 days (IQR 20-61) versus 50 days (IQR 43-68), P = 0.006]. One-year cumulative mortality was 8/27 (30%) in the TT group and 13/39 (33%) in the AC group (P = 0.46). There was one relapse in each group., Conclusion: Teicoplanin seems an effective treatment for selected patients with enterococcal IE, mainly to facilitate discharge., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. 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.)

Background: Infective endocarditis (IE) in children with pre-existing heart conditions is a life-threatening disease entity associated with significant morbidity and mortality. In our cardiac setting, the management outcomes of children with IE are not well documented. We therefore aimed to document the clinical profile and treatment outcomes of children with IE attended at the Jakaya Kikwete Cardiac Institute (JKCI)., Methods: This was a hospital-based cross-sectional study with longitudinal follow-up conducted among children with IE diagnosed by Modified Duke's Criteria at the JKCI from November 2021 to November 2023. A structured questionnaire was used to collect patients' socio-demographic and clinical data., Results: During the study period, 1,546 children were admitted to the JKCI. A total of 30 children with IE were enrolled, of these half (n = 16, 53%) were aged 10 to 18 years, with a median of 10 yrs (Inter quartile range, IQR: 6.5-12.2 yrs). Twelve children (40%) and nearly half (n = 14, 47%) had fever and used antibiotic therapy respectively. Majority of participants had anaemia (n = 26, 87%) and heart failure (n = 21, 70%). Nine children (30%) had positive blood cultures and S. aureus was the most frequently isolated organism (n = 7). Ten patients (33%) developed acute kidney injury (AKI), and eleven (37%) children died during the hospital stay., Conclusion: In our setting, in-hospital mortality due to IE among children with heart diseases is high. Heart failure and anaemia were the common presentations of IE. Furthermore, AKI was observed to be the leading in-hospital non-cardiac complication., (© 2024. The Author(s).)

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.)

Objectives: To investigate clinical outcomes of patients with Pseudomonas endocarditis and identify factors associated with treatment failure., Methods: Adult patients meeting definitive Duke's criteria for Pseudomonas endocarditis at 11 hospitals were identified between May 2000 and February 2024. Failure was defined as death or microbiological failure by day 42. First-line therapy consisted of cefepime, piperacillin/tazobactam, ceftazidime or ceftolozane/tazobactam alone or in combination., Results: Forty-eight patients met inclusion criteria; 29% were persons who inject drugs and 13% were organ transplant recipients. Pseudomonas aeruginosa was the causative species in 98% of cases. Patients who experienced 42 day cure were more likely to be initially managed with first-line β-lactam agents compared with those who experienced clinical failure (97% versus 62%, P = 0.004). Treatment with first-line β-lactams was associated with shorter time to treatment initiation and a lower likelihood of infection due to MDR Pseudomonas spp. In the univariate model, patients who experienced 90 day mortality were more likely to have prosthetic valve endocarditis (57% versus 24%, P = 0.02), an intracardiac complication (36% versus 9%, P = 0.04) and a higher median (IQR) Pitt bacteraemia score [2.5 (2-3.8) versus 1 (0-2), P = 0.048]. Combination therapy did not improve clinical outcomes but did increase the rate of adverse effects resulting in drug discontinuation compared with monotherapy, (21% versus 0%, P = 0.08)., Conclusions: This is the largest study of Pseudomonas endocarditis to date. We identified improved clinical outcomes when cefepime, piperacillin/tazobactam, ceftazidime or ceftolozane/tazobactam were used for initial treatment. We did not identify a clinical benefit for combination treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. 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.)

Purpose: To compare the effectiveness and safety of cefazolin versus cloxacillin for the treatment of infective endocarditis (IE) due to methicillin-sensitive Staphylococci (MSS)., Methods: Data were retrospectively collected on patients treated for a definite MSS endocarditis who received cefazolin or cloxacillin for at least 10 consecutive days in six French hospitals between January-1 2014 and December-31 2020. The primary endpoint was treatment failure defined as a composite of death within 90 days of starting antibiotherapy, or embolic event during antibiotherapy, or relapse of IE within 90 days of stopping antibiotherapy. We used Cox regression adjusted for the inverse probability of treatment weighting of receiving cefazolin., Results: 192 patients were included (median age 67.8 years). IE was caused by S.aureus in 175 (91.1%) and by coagulase-negative staphylococci in 17 (8.9%). Ninety-four patients (48.9%) received cefazolin, and 98 (51%) received cloxacillin. 34 patients (34.7%) with cefazolin and 26 (27.7%) with cloxacillin met the composite primary endpoint, with no significant differences between groups (adjusted HR = 1.13, 95% CI 0.63 to 2.03). There were no significant differences in secondary efficacy endpoints or biological safety events., Conclusion: The effectiveness of cefazolin did not significantly differ from cloxacillin for the treatment of MSS endocarditis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Infective endocarditis is a rare but potentially severe disease, associated with significant morbidity and mortality. Our study aims to describe the epidemiology and management aspects of endocarditis in northern Morocco and compare it with international management guidelines., Materials and Methods: This is a retrospective study involving all patients hospitalized in the cardiology department of the University Hospital of Tangier for infective endocarditis over a period of 4 years and 7 months, from May 2019 to February 2024., Results: Eighty patients were hospitalized for IE during the study period. The average age of the patients was 46 years, with an even sex ratio. IE concerned native valves in 77% of cases, mechanical prostheses in 19% of cases, and on bio prostheses in 4%. The average diagnostic delay was 25 days. Blood cultures were negative in 59% of cases. The predominant infective microorganism was the bacteria Staphylococcus (65.6%). Imaging results showed vegetations in 76.3% of cases, predominantly on the mitral valve (39.3%), followed by the aortic valve (21.3%). The main complications included heart failure (51.2%), peripheral arterial embolisms (22.5%) and splenic infarction (17.5%). Management wise, the most commonly used antibiotic therapy was a combination of ceftriaxone and gentamicin. Clinical and biological improvement was observed in 70% of cases, with a mortality rate of 12.5%. Twelve patients underwent surgery (15%). Urgent surgery was indicated in 66,7% of the operated patients., Conclusion: Our study highlights the challenges in managing infective endocarditis in northern Morocco. The prognosis of infective endocarditis can be improved through multidisciplinary management within the implementation of an Endocarditis Team., (© 2024. The Author(s).)

Abstract: Current data on the frequency and efficacy of linezolid (LNZ) in infective endocarditis (IE) are based on small retrospective series. We used a national database to evaluate the effectiveness of LNZ in IE.This is a retrospective study of IE patients in the Spanish GAMES database who received LNZ. We defined 3 levels of therapeutic impact: LNZ < 7 days, LNZ high-impact (≥ 7 days, > 50% of the total treatment, and > 50% of the LNZ doses prescribed in the first weeks of treatment), and LNZ ≥ 7 days not fulfilling the high-impact criteria (LNZ-NHI). Effectiveness of LNZ was assessed using propensity score matching and multivariate analysis of high-impact cases in comparison to patients not treated with LNZ from the GAMES database matched for age-adjusted comorbidity Charlson index, heart failure, renal failure, prosthetic and intracardiac IE device, left-sided IE, and Staphylococcus aureus. Primary outcomes were in-hospital mortality and one-year mortality. Secondary outcomes included IE complications and relapses.From 3467 patients included in the GAMES database, 295 (8.5%) received LNZ. After excluding 3 patients, 292 were grouped as follows for the analyses: 99 (33.9%) patients in LNZ < 7 days, 11 (3.7%) in LNZ high-impact, and 178 (61%) in LNZ-NHI. In-hospital mortality was 51.5%, 54.4%, and 19.1% respectively. In the propensity analysis, LNZ high-impact group presented with respect to matched controls not treated with LNZ higher in-hospital mortality (54.5% vs 18.2%, P = .04). The multivariate analysis showed an independent relationship of LNZ use with in-hospital mortality (odds ratio 9.06, 95% confidence interval 1.15--71.08, P = .03).Treatment with LNZ is relatively frequent, but most cases do not fulfill our high-impact criteria. Our data suggest that the use of LNZ as definitive treatment in IE may be associated with higher in-hospital mortality., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Streptococci still represent common etiologic agents of infective endocarditis (IE). Although renal failure is frequently reported as an aminoglycoside-associated adverse event, last international guidelines recommend a beta-lactam/gentamicin combination therapy. We retrospectively evaluated the use of daptomycin-based aminoglycoside-sparing combination therapy for the treatment of streptococcal IE in seven referral hospitals in Italy. Retrospective, multicenter, observational study. All patients with streptococcal IE admitted from 2016 to 2018 were enrolled. Mortality and incidence of acute kidney injury (AKI) were compared between Group A (standard of care, SoC) and Group B (daptomycin-based aminoglycoside-sparing combination therapy). Fifty-four patients were enrolled, 33 in Group A and 21 in Group B. Mortality was 2/33 (6%) in Group A and 0 in Group B ( p  = 0.681); AKI incidence was 8/33 (24%) in Group A and 0 in Group B ( p  = 0.04). Daptomycin-based aminoglycoside-sparing combination therapy appears to be promising for the treatment of streptococcal endocarditis because of similar efficacy compared with SoC and significantly reduced incidence of AKI.

Infective Endocarditis (IE) carries significant mortality. Bacteremia, which is a predisposing factor for IE, occurs more frequently in immunocompromised individuals. Interestingly, IE in kidney transplant recipients has not been adequately described. The aim of this study was to systematically review all published cases of IE in kidney transplant recipients and describe their epidemiology, microbiology, clinical characteristics, treatment and outcomes. A systematic review of PubMed (through 13 th December 2019) for studies providing epidemiological, clinical, microbiological as well as treatment data and outcomes of IE in kidney transplant recipients was performed. A total of 60 studies, containing data of 117 patients, were included in the analysis. The most common causative pathogens were gram-positive microorganisms in 57.4%, gram-negative microorganisms in 14.8%, fungi in 20%, while in 18.9% of cases, IE was culture-negative. Aortic valve was the most commonly infected valve followed by mitral, tricuspid and the pulmonary valve. Diagnosis was set with a transthoracic ultrasound in half the cases, followed by transesophageal ultrasound and autopsy. Fever was present in most cases, while embolic phenomena were noted in two out of five cases. Aminoglycosides, cephalosporins and aminopenicillins were the most commonly used antimicrobials, and surgical management was performed in one out of three cases. Clinical cure was noted in 60.9%, while overall mortality was 45.3%. To conclude, this systematic review thoroughly describes IE in kidney transplant recipients and provides information on epidemiology, clinical presentation, treatment and outcomes. Moreover, it identifies the emerging role of Enterococci , gram-negatives and fungi in IE in this population.

Background: A retrospective study of medically treated isolated left-sided infective endocarditis (LSIE) patients identifying predictors of outcomes with nonoperative management was undertaken., Methods: Medical records of 135 Manitoban medically managed LSIE patients from January 2004 to December 2016 were reviewed. Five-year survival for 135 patients and hospitalization data till March 2016 for 65 patients were collected from the Manitoba Centre for Health Policy., Results: In-hospital mortality was 44%. Patients with surgical indications were more likely to die in-hospital than those without (53% vs 24%; P = 0.002). Survival at 1 and 5 years was 43% and 23%, respectively. All-cause readmission at 1 and 5 years was 64% and 84%, respectively. At 1 and 5 years, readmission from major adverse events (heart failure, stroke, endocarditis) was 25% and 47%, and from recurrent endocarditis was 17% and 26%, respectively. Severe valvular regurgitation was a risk factor for in-hospital mortality (odds ratio, 3.52; P = 0.022), poor long-term survival (hazard ratio [HR], 2.57; P < 0.001), and recurrent endocarditis (HR, 5.93; P < 0.001). Prosthetic valve endocarditis was a risk factor for poor long-term survival (HR, 2.11; P = 0.002). Streptococcus viridans group was associated with better rates of in-hospital mortality (odds ratio, 0.28; P = 0.018) and long-term survival (HR, 0.34; P < 0.001)., Conclusions: Nonoperative management of LSIE carries a poor prognosis but may have a role in select cases. Surgical management remains the mainstay for patients with clear surgical indications, including severe regurgitation and prosthetic valve endocarditis. Further prospective analyses are required to better delineate appropriate patient selection for nonsurgical management., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Infective endocarditis is a microbial infection of the endocardial surface of the heart. Antibiotics are the cornerstone of treatment, but due to the differences in presentation, populations affected, and the wide variety of micro-organisms that can be responsible, their use is not standardised. This is an update of a review previously published in 2016., Objectives: To assess the existing evidence about the clinical benefits and harms of different antibiotics regimens used to treat people with infective endocarditis., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase Classic and Embase, LILACS, CINAHL, and the Conference Proceedings Citation Index - Science on 6 January 2020. We also searched three trials registers and handsearched the reference lists of included papers. We applied no language restrictions., Selection Criteria: We included randomised controlled trials (RCTs) assessing the effects of antibiotic regimens for treating definitive infective endocarditis diagnosed according to modified Duke's criteria. We considered all-cause mortality, cure rates, and adverse events as the primary outcomes. We excluded people with possible infective endocarditis and pregnant women., Data Collection and Analysis: Two review authors independently performed study selection, 'Risk of bias' assessment, and data extraction in duplicate. We constructed 'Summary of findings' tables and used GRADE methodology to assess the quality of the evidence. We described the included studies narratively., Main Results: Six small RCTs involving 1143 allocated/632 analysed participants met the inclusion criteria of this first update. The included trials had a high risk of bias. Three trials were sponsored by drug companies. Due to heterogeneity in outcome definitions and different antibiotics used data could not be pooled. The included trials compared miscellaneous antibiotic schedules having uncertain effects for all of the prespecified outcomes in this review. Evidence was either low or very low quality due to high risk of bias and very low number of events and small sample size. The results for all-cause mortality were as follows: one trial compared quinolone (levofloxacin) plus standard treatment (antistaphylococcal penicillin (cloxacillin or dicloxacillin), aminoglycoside (tobramycin or netilmicin), and rifampicin) versus standard treatment alone and reported 8/31 (26%) with levofloxacin plus standard treatment versus 9/39 (23%) with standard treatment alone; risk ratio (RR) 1.12, 95% confidence interval (CI) 0.49 to 2.56. One trial compared fosfomycin plus imipenem 3/4 (75%) versus vancomycin 0/4 (0%) (RR 7.00, 95% CI 0.47 to 103.27), and one trial compared partial oral treatment 7/201 (3.5%) versus conventional intravenous treatment 13/199 (6.53%) (RR 0.53, 95% CI 0.22 to 1.31). The results for rates of cure with or without surgery were as follows: one trial compared daptomycin versus low-dose gentamicin plus an antistaphylococcal penicillin (nafcillin, oxacillin, or flucloxacillin) or vancomycin and reported 9/28 (32.1%) with daptomycin versus 9/25 (36%) with low-dose gentamicin plus antistaphylococcal penicillin or vancomycin; RR 0.89, 95% CI 0.42 to 1.89. One trial compared glycopeptide (vancomycin or teicoplanin) plus gentamicin with cloxacillin plus gentamicin (13/23 (56%) versus 11/11 (100%); RR 0.59, 95% CI 0.40 to 0.85). One trial compared ceftriaxone plus gentamicin versus ceftriaxone alone (15/34 (44%) versus 21/33 (64%); RR 0.69, 95% CI 0.44 to 1.10), and one trial compared fosfomycin plus imipenem versus vancomycin (1/4 (25%) versus 2/4 (50%); RR 0.50, 95% CI 0.07 to 3.55). The included trials reported adverse events, the need for cardiac surgical interventions, and rates of uncontrolled infection, congestive heart failure, relapse of endocarditis, and septic emboli, and found no conclusive differences between groups (very low-quality evidence). No trials assessed quality of life., Authors' Conclusions: This first update confirms the findings of the original version of the review. Limited and low to very low-quality evidence suggests that the comparative effects of different antibiotic regimens in terms of cure rates or other relevant clinical outcomes are uncertain. The conclusions of this updated Cochrane Review were based on few RCTs with a high risk of bias. Accordingly, current evidence does not support or reject any regimen of antibiotic therapy for the treatment of infective endocarditis., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Purpose: Infective endocarditis (IE) is a severe infection, and a leading cause of mortality and morbidity. Due to its favourable microbiological and pharmacological characteristics, daptomycin is routinely used in clinical practice for treating IE., Methods: A prospective study was conducted at a large tertiary-care hospital in Italy over an 8-year period (January 2010-January 2018) on all patients with native-valve endocarditis (NVE) or prosthetic-valve endocarditis (PVE) caused by Gram-positive bacteria. Patients with NVE and PVE treated with regimens that included daptomycin at different dosages (daptomycin-containing regimens, DCR) were compared with those treated with non-DCR. Primary endpoints of the study were 30-day mortality and clinical treatment failure., Results: During the study period, 327 patients with Gram-positive NVE (n = 224, 68.8%) or PVE (n = 103, 31.2%) were analysed. Eighty-four (37.5%) NVE patients were treated with daptomycin, alone (59.9%) or with other antimicrobials. Most PVE patients (n = 61, 58%) were treated with a DCR, which always consisted of daptomycin plus other drugs. Among PVE patients, treatment with a DCR was associated with lower 30-day mortality than treatment with a non-DCR (6.5% vs. 38%, P < 0.001). Among NVE patients treated with DCRs, risk factors for 30-day mortality were streptococcal infections, persistent bacteraemia, and standard-dose (4-6 mg/kg) rather than high-dose daptomycin therapy. Overall, surgical treatment of IE and DCR were associated with clinical success and 30-day survival., Conclusions: Compared with non-DCRs, using single-drug or multiple-drug DCRs is associated with lower 30-day mortality in PVE, but with higher 30-day mortality in NVE at approved doses and in a subgroup of streptococcal IE., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

This study aimed to evaluate the effectiveness and safety of teicoplanin for treating enterococcal infective endocarditis (EIE). A retrospective analysis of a prospective cohort of definite EIE patients treated with teicoplanin in a Spanish referral centre (2000-2017) was performed. The primary outcome was mortality during treatment. Secondary outcomes were mortality during 3-month follow-up, adverse effects and relapse. A total of 22 patients received teicoplanin, 9 (40.9%) as first-line (8 Enterococcus faecium and 1 Enterococcus faecalis) and 13 (59.1%) as salvage therapy (13 E. faecalis). Median (IQR) age was 71.5 (58.3-78) years and Charlson comorbidity index was 4.5 (3-7). Five (22.7%) affected prosthetic valves. Median duration of treatment in survivors was 53 (42.5-61) days for antibiotics and 27 (17-41.5) days for teicoplanin [median dose 10 (10-10.8) mg/kg/day]. Reasons for teicoplanin use were resistance to β-lactams (40.9%), adverse events with previous regimens (31.8%) and outpatient parenteral antimicrobial therapy (OPAT) (27.3%). Teicoplanin was withdrawn due to adverse events in 2 patients (9.1%). Five patients (22.7%) died during treatment: four in the first-line (three with surgery indicated but not performed) and one in the salvage therapy group (surgery indicated but not performed). Two deaths (11.8%) occurred over the 3-month follow-up. There were no relapses during a median of 43.2 (22.1-69.1) months. Teicoplanin can be used as an alternative treatment for susceptible E. faecium IE and as a salvage therapy in selected patients with E. faecalis IE when adverse events develop with standard regimens or to allow OPAT., (Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Background: Patients with infective endocarditis on the left side of the heart are typically treated with intravenous antibiotic agents for up to 6 weeks. Whether a shift from intravenous to oral antibiotics once the patient is in stable condition would result in efficacy and safety similar to those with continued intravenous treatment is unknown., Methods: In a randomized, noninferiority, multicenter trial, we assigned 400 adults in stable condition who had endocarditis on the left side of the heart caused by streptococcus, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci and who were being treated with intravenous antibiotics to continue intravenous treatment (199 patients) or to switch to oral antibiotic treatment (201 patients). In all patients, antibiotic treatment was administered intravenously for at least 10 days. If feasible, patients in the orally treated group were discharged to outpatient treatment. The primary outcome was a composite of all-cause mortality, unplanned cardiac surgery, embolic events, or relapse of bacteremia with the primary pathogen, from the time of randomization until 6 months after antibiotic treatment was completed., Results: After randomization, antibiotic treatment was completed after a median of 19 days (interquartile range, 14 to 25) in the intravenously treated group and 17 days (interquartile range, 14 to 25) in the orally treated group (P=0.48). The primary composite outcome occurred in 24 patients (12.1%) in the intravenously treated group and in 18 (9.0%) in the orally treated group (between-group difference, 3.1 percentage points; 95% confidence interval, -3.4 to 9.6; P=0.40), which met noninferiority criteria., Conclusions: In patients with endocarditis on the left side of the heart who were in stable condition, changing to oral antibiotic treatment was noninferior to continued intravenous antibiotic treatment. (Funded by the Danish Heart Foundation and others; POET ClinicalTrials.gov number, NCT01375257 .).

Purpose: To analyze the influence of adding gentamicin to a regimen consisting of β-lactam or vancomycin plus rifampicin on survival in patients suffering from Staphylococcal prosthetic valve endocarditis (SPVE)., Methods: From January 2008 to September 2016, 334 patients with definite SPVE were attended in the participating hospitals. Ninety-four patients (28.1%) received treatment based on β-lactam or vancomycin plus rifampicin and were included in the study. Variables were analyzed which related to patient survival during admission, including having received treatment with gentamicin., Results: Seventy-seven (81.9%) were treated with cloxacillin (or vancomycin) plus rifampicin plus gentamicin, and 17 patients (18.1%) received the same regimen without gentamicin. The causative microorganism was Staphylococcus aureus in 40 cases (42.6%) and coagulase-negative staphylococci in 54 cases (57.4%). Overall, 40 patients (42.6%) died during hospital admission, 33 patients (42.9%) in the group receiving gentamicin and 7 patients in the group that did not (41.2%, P = 0.899). Worsening renal function was observed in 42 patients (54.5%) who received gentamicin and in 9 patients (52.9%) who did not (p = 0.904). Heart failure as a complication of endocarditis (OR: 4.58; CI 95%: 1.84-11.42) and not performing surgery when indicated (OR: 2.68; CI 95%: 1.03-6.94) increased mortality. Gentamicin administration remained unrelated to mortality (OR: 1.001; CI 95%: 0.29-3.38) in the multivariable analysis., Conclusions: The addition of gentamicin to a regimen containing vancomycin or cloxacillin plus rifampicin in SPVE was not associated to better outcome., (Copyright © 2018. Published by Elsevier Ltd.)

Objectives: Left-sided methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis treated with cloxacillin has a poorer prognosis when the vancomycin minimum inhibitory concentration (MIC) is ≥1.5 mg/L. We aimed to validate this using the International Collaboration on Endocarditis cohort and to analyse whether specific genetic characteristics were associated with a high vancomycin MIC (≥1.5 mg/L) phenotype., Methods: All patients with left-sided MSSA infective endocarditis treated with antistaphylococcal β-lactam antibiotics between 2000 and 2006 with available isolates were included. Vancomycin MIC was determined by Etest as either high (≥1.5 mg/L) or low (<1.5 mg/L). Isolates underwent spa typing to infer clonal complexes and multiplex PCR for identifying virulence genes. Univariate analysis was performed to evaluate the association between in-hospital and 1-year mortality, and vancomycin MIC phenotype., Results: Sixty-two cases met the inclusion criteria. Vancomycin MIC was low in 28 cases (45%) and high in 34 cases (55%). No significant differences in patient demographic data or characteristics of infection were observed between patients with infective endocarditis due to high and low vancomycin MIC isolates. Isolates with high and low vancomycin MIC had similar distributions of virulence genes and clonal lineages. In-hospital and 1-year mortality did not differ significantly between the two groups (32% (9/28) vs. 27% (9/34), p 0.780; and 43% (12/28) vs. 29% (10/34), p 0.298, for low and high vancomycin MIC respectively)., Conclusions: In this international cohort of patients with left-sided MSSA endocarditis treated with antistaphylococcal β-lactams, vancomycin MIC phenotype was not associated with patient demographics, clinical outcome or virulence gene repertoire., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: Infective endocarditis (IE) carries a high risk of cardiac morbidity and mortality, despite advances in the contemporary armamentarium. Along with the development of antibiotic resistant strains, research focusing on the efficacy of novel agents other than standard antibiotic regimens continues. Daptomycin, one of these antibiotics, is approved for the treatment of Staphylococcus bacteremia and right-sided endocarditis. This retrospective study was an investigation of the effectiveness of daptomycin in patients with left-sided IE., Methods: Fourteen patients (mean age 50.9±16.5; range 24 to 70 years) with the diagnosis of left-sided IE based on modified Duke criteria received daptomycin as monotherapy. Outcome was evaluated according to clinical improvement, microbiological eradication, and in-hospital mortality., Results: Blood culture was positive in 13 patients (92.8%) and staphylococci were isolated in all but 1 patient (92.3%). Daptomycin was administered as monotherapy at a dose of 6 or 8 mg/kg/day for mean of 40.6±4.4 days. Clinical recovery rate was 71.4% and microbiological eradication rate was 85.7%. Mean duration of clinical recovery was 8.7±3.2 days and duration of microbiological eradication was 11.1±3.6 days. Side effects developed in 6 patients, but drug discontinuation was not required in any patient. Ten patients improved without complications. Two patients were lost due to heart failure and multiple-organ failure while treatment was continuing, and 2 patients died in early cardiac postoperative period., Conclusion: Daptomycin is an effective and safe alternative to standard antibiotic therapy for the treatment of left-sided IE.

Aminoglycosides are a mainstay of treatment for enterococcal infective endocarditis. However, the benefit of adding aminoglycosides to cell wall-active agents after surgery is unclear. The aim of this study was to determine if adjunctive aminoglycoside treatment after surgery for enterococcal endocarditis leads to better outcomes. We included patients who underwent surgery for enterococcal endocarditis at our institution between July 2007 and July 2014. Treatment was defined as at least 1 dose of an aminoglycoside after surgery. Propensity to receive aminoglycosides was calculated in a model that included age, native vs prosthetic valve endocarditis, chronic kidney disease, high-level aminoglycoside resistance, metastatic infection, invasive disease, positive valve culture, and creatinine on the day of surgery. A multivariable Cox proportional hazards model was used to compare the primary outcome of death, adjusted for propensity to receive aminoglycosides, among patients who did and did not receive aminoglycosides. A total of 108 patients were identified of whom 37 (34%) received at least 1 dose of an aminoglycoside after surgery, with a median duration of 5 days (interquartile range: 2.5-10). In the multivariable model, patients treated with adjunctive aminoglycoside therapy had better survival than those treated with a cell wall-active agent alone, although the difference did not reach statistical significance (hazard ratio = 0.65, 95% CI: 0.32-1.33). The survival difference was consistently present in subgroups stratified by all-purpose refined diagnosis-related group mortality risk, and with varying definitions of aminoglycoside therapy. In conclusion, antibiotic monotherapy with a cell wall-active agent after surgery for enterococcal endocarditis may be inferior to combination therapy including an aminoglycoside., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Rifampin is recommended as adjunctive treatment for staphylococcal prosthetic valve endocarditis (PVE). It is unclear whether this should hold for surgically treated patients. The purpose of this study was to examine whether adjunctive rifampin treatment in addition to cell wall active antimicrobial agents in patients with surgically treated staphylococcal infective endocarditis (IE) results in better outcomes., Methods: Patients operated on for staphylococcal IE from April 1, 2008, to July 1, 2014, were identified from our institution's IE registry. Rifampin treatment was defined as 3 or more days of rifampin postoperatively. Cox proportional hazards regression was used to compare a composite outcome of death or reoperation for IE relapse, between patients treated and not treated with rifampin, adjusted for propensity to be treated with rifampin, methicillin resistance, all-purpose refined diagnosis related group (APR-DRG) severity score, and APR-DRG mortality risk., Results: In all, 273 patients were identified. The mean age was 56 years, 66% were male, 50% had PVE, 60% had S. aureus or S. lugdunensis infection, 89% had left side involvement, and 57% had invasive disease. Fifty-one (27%) received 3 or more days of rifampin postoperatively. Ninety-two patients died or underwent reoperation for IE relapse at a median of 205 days (interquartile range 56 to 718 days). In a multivariable model, patients treated with rifampin had a similar hazard of death or reoperation for IE relapse as those not treated (hazard ratio 0.76, 95% confidence interval 0.44 to 1.32, p value 0.34). The results were robust to varying definitions of rifampin treatment., Conclusions: Among patients with surgically treated staphylococcal IE there was insufficient evidence to claim a reoperation-free survival benefit from treatment with rifampin. Rifampin should not be used as adjunctive therapy for staphylococcal IE in patients who have undergone surgical procedures for its treatment., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and infective endocarditis (IE) have become increasingly difficult to treat over the past decade, with suboptimal response rates of less than 50%. Although vancomycin and daptomycin are standard therapeutic options, treatment failures with either or both agents are common. Telavancin is a lipoglycopeptide antibiotic with activity against MRSA. In vitro, telavancin displays bactericidal activity and has lower minimum inhibitory concentrations to MRSA than vancomycin., Methods: We present a retrospective, case-series report of 14 patients treated with telavancin for refractory MRSA bacteremia with and without IE at our institution from 9 September 2010 to 2 April 2012., Results: Of the 14 patients who received telavancin for refractory MRSA bacteremia and IE, eight survived their inpatient admission and were able to be followed for 30 days. The overall survival rate was 57% (n = 8). Of the eight surviving patients, five were diagnosed with MRSA IE and the remaining three were diagnosed with complicated MRSA bacteremia. All six patients who did not survive the inpatient admission were diagnosed with left-sided IE involving the mitral valves., Conclusions: This retrospective case series provides clinical evidence for the use of telavancin as a treatment option for refractory MRSA bacteremia and IE. With limited effective agents in the treatment of MRSA-complicated bacteremia and IE, telavancin represents a potential treatment option. Further randomized, controlled trials are necessary to define the optimal role of telavancin in the treatment of MRSA bacteremia and IE.

While trained infectious diseases (ID) specialists are regularly involved in inpatient and outpatient care in the United States and Canada, these specialized services are only rarely established in Germany. This article aims to summarize the findings of numerous studies that investigated the impact of ID consultation services on patient care and outcome in patients suffering from infectious diseases. The strongest evidence for a clinical benefit is found in the context of Staphylococcus aureus bacteremia (SAB), where in-hospital- and day-30 mortality was significantly and consistently reduced by about 40% in patients that were evaluated and treated in cooperation with an ID physician. Furthermore, studies revealed that this effect was associated with an improved adherence to standards of care. Newer studies show a reduced length of hospital stay due to ID consultations, especially if patients are evaluated early in the course of their hospital stay. Of note, informal or curbside consultations do not seem to be equivalent to a formal ID consultation with bedside patient evaluation. Studies in other patient groups (solid organ transplant recipients or intensive care unit patients) or in the context of other infections (infective endocarditis, pneumonia, other bloodstream infections) also revealed positive effects of ID consultations. Higher rates of appropriate empirical and targeted antimicrobial treatments and de-escalation strategies due to successful pathogen identification were documented. These modifications resulted in lower treatment costs and decreased antimicrobial resistance development. Although there are methodological limitations in single studies, we consider the consistent and reproducible positive effects of ID consultations shown in studies in different countries and health care systems as convincing evidence for the improved quality of care and treatment outcomes in patients with infectious diseases. Thus, strong consideration should be given to establish ID consultation services in small and medium sized hospitals as well., (Copyright © 2015. Published by Elsevier GmbH.)

A 59-year-old Caucasian male presented with progressive dyspnea, arthralgias and fever for three days. A diastolic regurgitation murmur was detected in the aortic area. A transesophageal echocardiograph showed several vegetations and severe aortic regurgitation. Blood cultures yielded Neisseria gonorrhoeae beta-lactamase negative. The patient had not noticed any urogenital discomfort or urethral discharge. The patient successfully underwent surgery for septal abscess debridement. The patient received ceftriaxone 2 g bid for eight weeks and the clinical follow-up was uneventful. The review of the literature revealed a total of the 38 additional cases reported between 1980 and the present. The majority of the patients were young, male and with native valve involvement. There has been a clear tendency for left-sided valve involvement (especially in the aortic valve). All valve cultures were reported negative despite, in most cases, the marked tissue destruction. Polymerase chain reaction was performed in two patients and positive results were shown in both. Cultures of exudates from other locations were negative in most cases. One striking fact is the high proportion of patients who underwent surgery (72 %). Information regarding antibiotic sensitivity was available in 28 cases, with penicillin resistance reported in six patients (21 %) and intermediate sensitivity in four patients (14 %). Resistance to ciprofloxacin was reported in two cases (7 %). A rapid increase and distribution of isolates resistant to third generation cephalosporins have been recently detected. The mortality is high, particularly taking into account that most were young patients who had not presented previous heart disease.

Logistic regression is used to obtain odds ratio in the presence of more than one explanatory variable. The procedure is quite similar to multiple linear regression, with the exception that the response variable is binomial. The result is the impact of each variable on the odds ratio of the observed event of interest. The main advantage is to avoid confounding effects by analyzing the association of all variables together. In this article, we explain the logistic regression procedure using examples to make it as simple as possible. After definition of the technique, the basic interpretation of the results is highlighted and then some special issues are discussed.

Comparative analysis of anamnestic, clinical, laboratory and instrumental data involved 106 patients with infectious endocarditis treated in S.P. Botkin City Clinical Hospital in 2000-2011 and 92 ones admitted in 1985-1977. The results give evidence of ongoing pathomorphosis of infectious endocarditis as is apparent from the growing number of male patients, increased frequency of primary cases and previous invasive or intravascular manipulations, thromboembolic complications including pulmonary thromboembolism, right heart chamber endocarditis. Over half of the patients are socially unadapted C-peptide level is of diagnostic value for the assessment of inflammation activity, precursors of natriuretic peptide can be used to detect preclinical and clinical stages of cardiac failure related to infectious endocarditis. There is correlation between severity of inflammation and myocardial dysfunction. Early surgical intervention in the absence of effect of combined antibacterial therapy improves prognosis. Morphological studies of inflammation-related changes in myocardium, destruction of cardiomyocytes, dystrophic processes, and fibrosis play an important role in the development of cardiac insufficiency and prognosis of infectious endocarditis.

The aim of this study was to assess the impact of an operative protocol with a multidisciplinary approach on the outcome of patients with prosthetic valve endocarditis (PVE). A formal policy for the care of PVE was introduced at our hospital in 2003 in which patients were referred to and managed by a preexisting team involving a cardiologist, a specialist in infectious diseases, and a cardiac surgeon. All patients underwent transesophageal echocardiography as soon as clinical suspicion of PVE arose. If high-risk conditions such as heart failure, ring abscess, conditions associated with impending malfunctioning of the prosthesis, or vegetations at high risk for systemic embolization were found during the initial multidisciplinary evaluation (performed within 12 hours of admission), patients were operated on within 48 hours. Stable patients were evaluated weekly by the multidisciplinary team, and on-treatment surgery was performed whenever high-risk conditions developed or when there was persistent fever/bacteremia after 1 week of adequate antibiotic therapy. Comparing the period 2003 through 2009 with 1996 through 2002 (when a multidisciplinary policy was not followed), patients with PVE were more numerous (61 vs 38), older (mean age 68.3 vs 63.1, p = 0.01), and had more co-morbidities (mean Charlson index 3.15 vs 2.42, p = 0.03). The most frequent causative organisms were Staphylococci in both periods. In the second period, fewer patients had delayed diagnosis (39% vs 71%, p = 0.03), heart failure (20% vs 45%, p = 0.01), abscess (20% vs 39%, p = 0.04), culture-negative infective endocarditis (11% vs 29%, p = 0.03), and worsened renal function (21% vs 42%, p = 0.04). A significant reduction in in-hospital mortality (53% to 23%, p = 0.04) and 3-year mortality (60% to 28%, p = 0.001) was observed, driven by the increased number of patients successfully treated with medical therapy alone (44% vs 16%, p = 0.04). In conclusion, formalized, collaborative management led to significant improvement in PVE-related mortality., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background and Aim of the Study: Isolated bacterial tricuspid valve (TV) endocarditis is usually managed medically. Whilst the indications and optimal timing for surgical treatment of the condition have not been clearly defined, it is hypothesized that early surgery in patients who are bacteremic and/or have evidence of systemic seeding is superior to medical treatment., Methods: All cases of isolated TV endocarditis reported between 2006 and 2011 at the authors' institution were reviewed. Patients with bacteremia and/or systemic seeding who were treated surgically after short-term medical therapy were compared to an equivalent group of patients who remained under long-term medical treatment only., Results: A total of 45 patients with isolated TV endocarditis showed evidence of bacteremia and/or systemic seeding. Of these patients, 10 (22.2%) were treated surgically with valve repair or replacement, and 35 (77.8%) received long-term medical therapy only. The 30-day and one-year survival rates in both groups were comparable (100% versus 88.6%, p = 0.27). Patients treated surgically had clear blood cultures sooner (2.0 versus 6.7 days, p = 0.04), defervesced earlier (0 versus 9.0 days, p = 0.02), and demonstrated a complete resolution of TV vegetations (100% versus 30.0%, p = 0.003). Change in creatinine clearance (+22.1 versus +11.6 ml/min, p = 0.40) and durations of vasopressor support (6.8 versus 8.9 h, p = 0.86), mechanical ventilation (8.5 versus 32.2 h, p = 0.44), ICU stay (148.1 versus 53.8 h, p = 0.14) and total hospital stay (32.1 versus 24.6 days, p = 0.22) were not different between groups. Long-term echocardiogram surveillance demonstrated a higher prevalence of moderate-severe tricuspid regurgitation in the medically treated patients (75.0 versus 0.0%, p < 0.001). None of the patients treated surgically was readmitted with prosthetic valve endocarditis., Conclusion: Early surgery is warranted in patients with isolated TV endocarditis who are bacteremic and/or systemically infected despite optimal medical therapy.

Unlabelled: Infectious endocarditis (IE) represents a rare pathology in children, but with lethal potential. The goal of the therapy is fast and total eradication of the infection., Aims: To study particularities in diagnosis and treatment for infectious endocarditis in children., Material and Methods: Children with infectious endocarditis hospitalized between January 2007 - February 2012 in the Cardiology Department of the ,,Sfânta Maria" Children Emergency Hospital of lasi have been included in the study., Results: The patients are aged between 23 days and 16 years, the average age being 4 years old. At approximately 88% of the patients (14 cases), the endocardial damage appeared in the pre-existent valvular lesions, specially mitral and aortal. As associated congenital malformations, the patients prevailingly presented ventricular septal defect, mitral valve prolapse, arterial canal persistence, aortic stenosis, coarctation of the aorta. Blood cultures were collected and the most frequent identified etiological agents were: Staphylococcus coagulase-positive, Streptococcus mitis, Staphylococcus speciae coagulase-negative, Staphylococcus haemolyticus, Streptococcus bovis, Escherichia coli, for which the antibiogram showed sensitivity for beta-lactam, cephalosporins, glycopeptides, trimethoprim-sulfamethoxazole, rifampicin, quinolone, lincosamides, oxazolidinones, and thus specific treatment was set up according to the antibiogram., Conclusions: The infectious endocarditis is a serious disease that affects young age too, leading towards exitus in some cases. Diagnostic imaging and early blood cultures are of relevance in order to intervene promptly. The treatment must be targeted and applied as fast as possible.

Cardiac device infections (CDIs) represent a serious complication after the implantation of pacemakers and defibrillators. In addition to antimicrobials, complete hardware removal, mostly with percutaneous lead extraction (PLE), is necessary to limit recurrences. However, CDI diagnosis is often difficult and is sometimes delayed, and scarce data exist on how the timing of PLE may affect clinical outcomes. In this study, the in-hospital outcomes of 52 consecutive patients with CDIs who underwent PLE were retrospectively analyze. Co-morbidities such as diabetes mellitus, congestive heart failure, renal insufficiency, and end-stage renal disease were highly prevalent in the study cohort. Patients were divided into group A (bacteremia or device endocarditis) and group B (localized pocket infection). In-hospital mortality was 29% in group A and 5% in group B (p = 0.02) and was due mostly to sepsis. Hospital stays were shorter in group B patients (5.7 vs 21.7 days, p <0.001). Presentation with hypotension was more commonly observed in group A patients and was associated with higher in-hospital mortality, whereas pocket findings correlated with better survival. Postoperative courses after PLE were uneventful in most patients, and no fatal complications were observed. PLE was performed significantly earlier in group B patients (hospitalization day 1.3 vs 7.6, p <0.001). PLE performed within 3 hospitalization days was associated with lower in-hospital mortality (p = 0.01). In conclusion, PLE performed within 3 days from admission is associated with shorter hospitalization and better survival. A timely diagnosis is crucial, particularly in the absence of local findings, because early treatment with PLE is likely to prevent the catastrophic outcomes of unrelenting CDIs., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To assess long-term outcomes and predictors of mortality in patients treated according to current recommendations for cardiac implantable electronic device (CIED) infection., Design: Two-group matched cohort study., Setting: Tertiary-care institution., Patients: Consecutive patients admitted for CIED infection between 2004 and 2008 were prospectively enrolled. Study subjects were matched to a cohort of uninfected CIED patients by age, sex and type of device., Interventions: In all infected patients, the therapeutic approach consisted of complete hardware removal whenever possible, antimicrobial therapy, and implantation of a new device, if indicated. Patients were systematically followed, with standardised outcomes assessment., Main Outcome Measures: All-cause mortality and predictors of long-term mortality., Results: 197 patients were included and matched 1:1 to controls. Pocket infections were present in 41.1% and definite or suspected infective endocarditis in 58.9%. Total or subtotal hardware removal was achieved in 98.5% of cases. Median follow up was 25 months (12-70). Mortality rates in the study group and controls were 14.3% vs 11.0% (NS) at 1 year and 35.4% vs 27.0% (p=NS) at 5 years. Independent predictors of long-term mortality were older age (HR=1.09, p<0.001), cardiac resynchronisation therapy (HR=3.70, p=0.001), thrombocytopenia (HR=5.10, p=0.003) and renal insufficiency (HR=2.66, p=0.006). In patients with reimplanted devices, epicardial right ventricular pacemakers were associated with higher mortality (HR=2.85, p=0.034)., Conclusion: In patients with CIED infection managed by recommended therapy, long-term mortality rates are similar to comparable controls. Independent predictors include patient and disease-related factors, in addition to implantation of right ventricular epicardial pacemakers.

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of complicated bacteremia (CB) and infective endocarditis (IE). The gold standard treatment for these infections is vancomycin. A vancomycin area under the concentration-time curve from 0 to 24 h (AUC(24))/MIC ratio of >400 has been suggested as a target to achieve clinical effectiveness, and yet to date no study has quantitatively investigated the AUC(24)/MIC ratio and its association with attributable mortality (AM). We performed a review of patients treated for MRSA CB and IE from 1 July 2006 to 30 June 2008. AM was defined as deaths where CB or IE was documented as the main cause or was mentioned as the main diagnosis. Classification and regression tree analysis (CART) was used to identify the AUC(24)/MIC ratio associated with AM. Mann-Whitney and Fisher exact tests were used for univariate analysis, and logistic regression was used for multivariate modeling. The MICs were determined by Etest, and the AUC(24) was determined using a maximum a posteriori probability-Bayesian estimator. A total of 32 CB and 18 IE patients were enrolled. The overall crude mortality and AM were 24 and 16%, respectively. The CART-derived partition for the AUC(24)/MIC ratio and AM was <211. Patients with an AUC(24)/MIC ratio of <211 had a >4-fold increase in AM than patients who received vancomycin doses that achieved an AUC(24)/MIC ratio of ≥211 (38 and 8%, respectively; P = 0.02). In bivariate analysis the APACHE-II score and an AUC(24)/MIC ratio of <211 were significantly associated with AM. In the multivariate model, the APACHE-II score (odds ratio, 1.24; P = 0.04) and a vancomycin AUC/MIC ratio of <211 (odds ratio, 10.4; P = 0.01) were independent predictors of AM. In our analysis, independent predictors of AM were the APACHE-II score and an AUC(24)/MIC ratio of <211. We believe further investigations are warranted.

Purpose: Although limited data exist on the efficacy and potential risk of synergistic aminoglycoside therapy for persistent Staphylococcus aureus bacteremia and endocarditis, aminoglycosides are frequently used in clinical practice., Methods: As our study population, we included subjects fulfilling the modified Duke criteria for S. aureus endocarditis and/or having greater than 72 h of S. aureus bacteremia. Among these subjects, we compared patients who did and did not receive aminoglycoside therapy for their S. aureus bloodstream infection. These groups were compared for the primary outcome of recurrent bacteremia, as well as for the duration of bacteremia, mortality, complication rate, and incident renal failure., Results: Eighty-seven subjects fulfilled the inclusion criteria. Of these, 49 received aminoglycoside therapy, whereas 38 did not. There were no significant differences in the baseline characteristics when comparing groups who did or did not receive aminoglycoside therapy. Four (8.2%) subjects treated with aminoglycoside therapy experienced recurrent bacteremia versus nine (23.7%) who did not receive aminoglycoside therapy [relative risk and 95% confidence interval [RR (95%CI)] = 0.51 (0.22-1.17), p = 0.04]. In multivariable analyses, aminoglycoside use remained significantly associated with a decrease in recurrent bacteremia [adjusted odds ratio (OR) (95%CI) = 0.26 (0.07-0.98), p = 0.046]. No significant differences were seen between groups treated with and without an aminoglycoside in terms of the 6-month all-cause mortality (51.0 vs. 42.1%, p = 0.41), complication rate (71.4 vs. 73.7%, p = 0.82), or incident renal failure (54.5 vs. 46.9%, p = 0.54)., Conclusions: The use of combination therapy with an aminoglycoside in persistent S. aureus bacteremia and/or endocarditis may be associated with a lower rate of recurrent bacteremia without significant differences in the incident renal failure.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is the primary cause of complicated bacteremia (CB) and infective endocarditis (IE). Studies have compared the costs of treatment with vancomycin to those of other agents, as well as the efficacy and tolerability of these treatments. However, a literature search found no published studies of the effects of vancomycin exposure on outcomes and hospital costs in patients with CB or IE due to MRSA., Objective: The aim of this study was to determine whether there is a quantitative relationship between the duration of vancomycin treatment or cumulative vancomycin exposure and outcomes or costs in patient with CB or IE due to MRSA., Methods: Electronic medical records of confirmed cases of MRSA-related CB or IE from July 1, 2006, to June 30, 2008, were retrospectively reviewed to identify patients with a history of vancomycin exposure or no vancomycin exposure. Those who received vancomycin were stratified by the amount of drug administered or the duration of treatment to determine the relationship between treatment and outcomes. Data collected included demographic information, treatment information, attributable mortality, MIC data, and hospital costs. Classification and regression tree analysis (CART) was used to determine whether a history of vancomycin exposure was associated with treatment failure, attributable mortality, or both. The Mann-Whitney U test and the Fisher exact test were used for univariate analyses, and logistic regression was used for multivariate modeling., Results: Data from 50 patients were evaluated (CB, 32; IE, 18). Overall rates of failure and attributable mortality were 32% and 16%, respectively. No significant differences were observed between the variables and costs. The CART break points for failure were ≥18.75 g and ≥14 days of vancomycin treatment in the previous 3 years; for attributable mortality, the CART break points were ≥45 g and ≥31 days. In the final multivariate model for failure, ≥18.75 g and ≥14 days of vancomycin treatment in the previous 3 years were predictors of failure (both, P = 0.002). Acute Physiology and Chronic Health Evaluation (APACHE) II score (P = 0.04), ≥45 g (P = 0.002), and ≥31 days of treatment (P = 0.002) in the previous 3 years were predictors of attributable mortality after adjustment for all covariates., Conclusions: Using the present model, cumulative vancomycin amount and duration were associated with attributable mortality and clinical failure but not with costs., (Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.)

Background: Therapeutic use of vancomycin is characterized by decreased susceptibilities and increasing reports of clinical failures. Few studies have examined the clinical outcomes of patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia treated with vancomycin. The primary objective was to compare clinical outcomes of patients with MRSA bacteraemia treated according to standard of care practices., Methods: Patients were included if: (i) admitted to University of New Mexico Hospital between 2002 and 2009; (ii) ≥18 years of age; (iii) had one blood culture positive for MRSA; and (iv) received vancomycin. Clinical outcomes were defined as cure, failure (relapse of infection 30 days after completion of therapy, death or change in therapy) or unevaluable. Patient demographics, source of bacteraemia, treatment regimen, and microbiological characteristics were determined., Results: Two hundred patients with MRSA bacteraemia were included. Sixty-one patients were unevaluable, leaving 139 patients for the final analysis. Seventy-two (51.8%) patients were cured and 67 (48.2%) experienced vancomycin failure. Vancomycin MIC(90) was 2 mg/L for both groups by Etest. Patients with endocarditis (P = 0.02) or pneumonia (P = 0.02) were more likely to fail therapy. Panton-Valentine leucocidin, loss of agr functionality and strain type were not predictors of outcomes in this study., Conclusions: High failure rates were observed in patients with MRSA bacteraemia treated with vancomycin, despite high vancomycin troughs and low rates of nephrotoxicity. Predictors of vancomycin failure included endocarditis and pneumonia. In these situations, vancomycin provides suboptimal therapy.

Antibiotic treatment, surgical intervention and postoperative antibiotic regimens are recommended for the treatment of brucella endocarditis (BE). Our clinical antibiotic regimens involve a triple antibiotic regimen for treating BE before the operation. The combination of three antibiotics is continued for at least six months and until the titres of the Wright serologic test are diminished to 1:160 levels. In this study, our aim was to evaluate the effects of combined medical and surgical treatments on survival and relapse rates in the periods of mid to late terms. We investigated 13 patients who were treated between January 1993 and June 2009. Our clinical observations led us to use a combination of rifampicin (900 mg twice a day), streptomycin (12 to 16 mg/kg/24 h intramuscularly) and doxycycline (200 mg/kg twice a day); rifampicin, tetracycline (8 mg/kg three times a day) and cotrimoxazole (15 mg/kg twice a day) or rifampicin, doxycycline and cotrimoxazole regimen for treating BE before the operation. This treatment should be continued for at least six months after surgery in order to prevent relapses.

Despite the progress in medicine, infectious endocarditis is often diagnosed late, as its symptomatology is subject to a high variability. The clinical features are usually atypical. Since the introduction of the Duke criteria, clinical, bacteriological and echocardiographical findings are being integrated, allowing an earlier definitive diagnosis. The incidence remains practically stable. The decrease in post-rheumatic valvular heart disease at population level is compensated by an increase in degenerative valvular heart disease as predisposing factor. Moreover, the share of patients with intravascular foreign material is increasing. Endocarditis is usually characterized by a complicated development. About half of the patients develop heart failure as a consequence of the destruction of the affected valve with serious valvular insufficiency. One third of the patients present cerebral or peripheral embolization. Embolization predominantly occurs at the beginning, until the first two weeks of antibiotic treatment. Abscess formation occurs more frequently than is suspected based on echographical examinations. Particularly a Staphylococcus aureus infection in the presence of an artificial valve leads to extravalvular extension with abscess formation around the artificial valve. Treatment should be initiated promptly. High doses of antibiotics, tailored to the microorganism and the valve type (native or artificial valve), are administered intravenously during four, or more frequently, six weeks. In more than half of the patients cardiac surgery is also required. As soon as an indication for cardiac surgery is present, the operation should not be postponed. Experience learns that a smaller risk is associated with an early intervention. The operation is performed in a technically easier way. Eventually, also the total duration of hospitalization is shorter. Despite the available antibiotics and the technical progress in cardiac surgery, mortality remains high. This is the consequence of an increasing share of aggressive hospital germs, on the one hand, and an older population, characterized by a higher comorbidity, on the other hand.

Background: The enrollment of intravenous drug users (IVDUs) into an outpatient parenteral antibiotic treatment (OPAT) service using a peripherally inserted central catheter (PICC) is controversial and often avoided. The National University Hospital in Singapore has a policy of permitting OPAT-based treatment of IVDU patients with appropriate medical indications. We report on our experiences., Methods: A prospective observational study was conducted on IVDU patients requiring parenteral antibiotics via an OPAT service from January 2005 to December 2009. Clinically appropriate patients were screened using pre-defined criteria and enrolled into our service, where standardized measures were enforced to prevent and detect PICC abuse and optimize treatment. Outcomes measured included mortality, completion of therapy, PICC abuse, and readmission for infective or treatment-related complications during OPAT and a 30 day follow-up period., Results: Twenty-nine IVDU patients received treatment in our OPAT service (total 675 patient-days). The median duration of therapy was 18 days (range 1-85). Infective endocarditis was the primary diagnosis in 42% of cases. Two patients (7%) had recrudescent infection after absconding during their inpatient stay. These two patients subsequently completed treatment in OPAT. There were no deaths or cases of PICC abuse. Five patients (17%) during OPAT and one patient (3%) during the 30-day follow-up period required readmission for infective or treatment-related complications., Conclusions: Appropriately selected, counselled and monitored patients with a history of being an IVDU can be treated safely and successfully via OPAT centres. It is likely that some will respond better to treatment in an outpatient setting.

Background: Brucella endocarditis is a life-threatening complication of human brucellosis. In this study, our aim was to evaluate the effects of combined medical and surgical treatment in the midterm to long term., Methods: We retrospectively analyzed 13 patients (mean age 44 +/- 18 years; 8 males) who were operated on from January 1993 to June 2009. Duke criteria were used for the diagnosis of endocarditis. The primary endpoint was defined as the overall mortality and readmission to the hospital during early and late follow-up periods. The other collected data included baseline and follow-up clinical findings, along with echocardiographic and laboratory measurements., Results: No patients died in the early period (up to 1 month) and 2 patients (15.3%) died during the late follow-up period. Aortic valve disease was observed in 11 of 13 patients (85%). The most commonly performed procedure was aortic valve replacement (10 of 13 patients; 77%) during a mean follow-up period of 95 +/- 60 months (range, 10 to 184; median, 74)., Conclusions: For Brucella endocarditis, perioperative antibiotic therapy combined with surgical treatment (prosthetic valve replacement) has satisfactory results and increases the quality of life in the long-term follow-up., (Copyright (c) 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Brucellosis is frequently seen in Mediterranean and Middle East countries, including Turkey. We report the medical and surgical management of 31 cases of native endocarditis., Material and Method: Thirty-one patients were admitted to our clinic with suspected Brucella Endocarditis. The diagnosis was established by either isolation of Brucella species, or the presence of antibodies. Following preoperative antibiotic therapy patients underwent valve replacement with excessive tissue debridement. Patients were followed up with Brucella titers, blood cultures, and echocardiography., Results: On admission all patients were febrile and mostly dyspneic (NYHA Class 3 or 4). The blood tests were normal except for elevated ESR, CRP and serological tests. The aortic valve was involved in 19 patients, mitral valve in 7 patients, and both valves in 5. After serological confirmation of BE, antibiotic therapy was maintained. Twenty-five of the patients received rifampicine, doxycycline, and cotrimaxozole; 2 of them received a combination of rifampicine, streptomycin, and doxycycline; and 4 of them received rifampicine, tetracycline, and cotrimaxozole. Tissue loss in most of the affected leaflets and vegetations were presenting all patients. Valve replacements were performed with mechanical and biologic prostheses. All the patients were afebrile at discharge but received the antibiotics for 101, 2+/-16, 9 days. The follow-up was 37, 1+/-9, 2 months., Discussion: In our retrospective study, combination of adequate medical and surgical therapy resulted in declined morbidity and mortality rate. The valve replacement with aggressive debridement is the most important part of the treatment, which should be supported with efficient preoperative and long term postoperative medical treatment., (Copyright 2010 Wiley Periodicals, Inc.)

Objectives: To describe the use and outcomes of outpatient antimicrobial therapy (OPAT) for infective endocarditis (IE) within the Canterbury region of New Zealand over an 8 year period., Methods: All cases of IE admitted to Christchurch Hospital were reviewed. Prospectively collected data from our OPAT service's database and retrospective data from case notes were analysed., Results: There were 213 episodes of IE meeting modified Duke Criteria over this time. Patients received OPAT in 100 episodes. Viridans streptococci were the infecting organism in 34, Staphylococcus aureus in 27, and enterococci in 10. Adverse events were encountered in 27 episodes. Of these, 24 were related to intravenous lines, infusion devices or adverse drug reactions which resolved with change of treatment. There were 3 serious adverse events which were likely to have occurred in hospital. During 12-month follow-up there were 5 further episodes of IE and 2 deaths unlikely to be directly related to the episode of IE., Conclusions: Despite significant co-morbidities and complications, nearly half of all patients with IE, including those with disease due to S. aureus and enterococci, successfully completed their treatment as outpatients. Continuous infusion devices were successfully used in 32 patients, including 22 with disease due to S. aureus.

The complications from S. aureus bacteremia (SAB) and infective endocarditis (SAIE) are higher in patients with diabetes. We summarize the characteristics and outcome of diabetic patients enrolled in a multicenter trial of daptomycin vs. standard therapy for SAB and SAIE. Adult patients with SAB were randomized to daptomycin 6 mg/kg/day or standard therapy (vancomycin 1 g every 12 h or antistaphylococcal penicillin 2 g every 4 h, both with gentamicin 1 mg/kg every 8 h for 4 days). Clinical success was defined as survival, resolution of S. aureus infection, and clinical outcome of cure or improved 6 weeks after end of therapy. Diabetic patients (86/235) were older, more overweight, and were more likely to present with systemic inflammatory response syndrome (SIRS) and to have complicated SAB. Clinical success rates were similar (67.4% in diabetics and 70.5% in non-diabetics). The mortality rate was significantly higher among diabetic patients (22.1% vs. 11.4%, p = 0.038). In the diabetes subgroup, the clinical success and mortality rates were comparable between the daptomycin and the standard therapy arms. The presence of diabetes is associated with significantly higher mortality in patients with SAB and SAIE. Daptomycin is an alternative therapeutic option in diabetic patients with these serious staphylococcal infections.

Background: A large number of patients treated at our hospital for endocarditis have negative cultures. Taking into consideration the fact that many of these patients receive antibiotics prior to referral, we decided to study culture-negative endocarditis in Pakistan., Methods: The medical records of all patients admitted to the Aga Khan University Hospital, Pakistan, for the period from 1988 to 2001, with an underlying diagnosis of infective endocarditis (IE) and negative cultures, were reviewed., Results: Of the 159 patients diagnosed with IE by revised Duke criteria, 86 (54.1%) had persistent negative cultures. More than half of these patients (52%) had received antibiotics before being referred to our center. Patients with culture-negative endocarditis were less likely to be classified as definite endocarditis by revised Duke criteria (p<0.001, 95% CI 0.07-0.3) or to have large vegetations (p=0.021, 95% CI 0.05-0.5), and more likely to have a mitral valve prolapse (p=0.003, 95% CI 1.6-2.3). Definite endocarditis (p=0.042, 95% CI 1.02-7.4), heart failure (p=0.008, 95% CI 1.4-12.7), renal failure (p=0.017, 95% CI 1.16-40.7), embolism (p=0.019, 95% CI 1.2-38.8), and neurological complications (p=0.02, 95% CI 1.16-9.2) were associated with an increased mortality., Conclusion: Culture-negative endocarditis is very common among patients with IE in Pakistan. The presentation, laboratory findings, and complications are similar to those for culture-positive endocarditis. It is postulated that previous antibiotic treatment is the most common cause of culture-negative endocarditis in our hospital.

Infective endocarditis (IE) is the fourth leading cause of life-threatening infection in the United States and imposes significant morbidity and mortality. The American Heart Association guidelines for the diagnosis and treatment of IE do not address continuous-infusion (CI) oxacillin. This retrospective study compares outcomes between CI oxacillin and intermittent-infusion (II) oxacillin in the treatment of IE caused by methicillin-susceptible Staphylococcus aureus (MSSA). A total of 709 medical records were reviewed for inpatients with definitive IE treated between 1 January 2000 and 31 December 2007. Continuous data were analyzed by Student's t test or the Wilcoxon rank sum test. The chi-square test or Fisher's exact test was used to compare nominal data. A multivariate logistic model was constructed. One hundred seven patients met eligibility criteria for inclusion into the study. Seventy-eight patients received CI oxacillin, whereas 28 received II oxacillin. CI and II groups were similar with respect to 30-day mortality (8% versus 10%, P = 0.7) and length of stay (20 versus 25 days, P = 0.4) but differed in 30-day microbiological cure (94% versus 79%, P = 0.03). Sixty-three patients received synergistic gentamicin, whereas 44 did not. The gentamicin and no-gentamicin groups were similar with respect to 30-day mortality (11% versus 4%, P = 0.2) and 30-day microbiological cure (90% versus 89%, P = 0.8); however, times to defervescence (4 versus 2 days, P = 0.02) were significantly different. CI oxacillin is an effective alternative to II oxacillin for the treatment of IE caused by MSSA and may improve microbiological cure. This convenient and pharmacodynamically optimized dosing regimen for oxacillin deserves consideration for patients with IE caused by MSSA.

Moxifloxacin (MXF) is an 8-methoxyquinolone with high activity against Gram-positive bacteria. In an experimental model of aortic valve endocarditis (EAVE), the efficacy of MXF was evaluated against a strain of methicillin-resistant Staphylococcus aureus (MRSA). Rabbits with catheter-induced aortic valve vegetations were randomly assigned to a control group or to groups receiving MXF 20 mg/kg intravenous (i.v.) twice a day (bid) or vancomycin (VAN) 30 mg/kg i.v. bid for a total of eight doses (4 days). Rabbits were sacrificed 15 h after the last dose of antibiotics. In another group, treatment with MXF was extended to 5 days and rabbits were sacrificed 5 days after the last dose (10th dose) of MXF in order to detect possible relapses of endocarditis after the end of treatment (test-of-cure (TOC) study). Both MXF and VAN significantly reduced the bacterial load in vegetations (P < 0.001 vs. controls). All animals in the MXF-TOC group had sterile vegetations. MXF given at a dose of 20 mg/kg i.v. bid for 4 days was equally effective as VAN in the treatment of EAVE due to MRSA. When treatment with MXF was extended to 5 days, the cure rate reached 100% and no relapses of endocarditis were observed.

110 drug addicted patients with infectious endocarditis (IE), 67 males and 43 females with average age 24 +/- 3.2 years were examined. Positive results of conservative therapy were in 69.2% patients with isolated lesion of tricuspid valve. Hospital lethality in the group of patients was 35.5% (39 cases). The analysis of survival rate of IE patients with the use of Cox's regression model made possible to establish that main predictors of lethal outcome in the group of patients were dimensions of microbe vegetations on tricuspid valve more than 2 cm, development of acute left ventricle failure, DIC-syndrome, and high degree tricuspid valve failure. Presence of HIV in early stage and C hepatitis without clinical laboratory activity did not have significant influence on IE outcome in this group of patients.