AUC/MIC Pharmacodynamic Target Is Not a Good Predictor of Vancomycin Efficacy in Methicillin-Resistant Staphylococcus aureus Experimental Endocarditis.

The aim of this in vivo study was to compare the efficacy of vancomycin at standard doses (VAN-SD) to that of VAN at adjusted doses (VAN-AD) in achieving a VAN area under the curve/MIC ratio (AUC/MIC) of ≥400 against three methicillin-resistant Staphylococcus aureus (MRSA) strains with different microdilution VAN MICs in an experimental endocarditis model. The valve vegetation bacterial counts after 48 h of VAN therapy were compared, and no differences were observed between the two treatment groups for any of the three strains tested. Overall, for VAN-SD and VAN-AD, the rates of sterile vegetations were 15/45 (33.3%) and 21/49 (42.8%) (P = 0.343), while the medians (interquartile ranges [IQRs]) for log10 CFU/g of vegetation were 2 (0 to 6.9) and 2 (0 to 4.5) (P = 0.384), respectively. In conclusion, this VAN AUC/MIC pharmacodynamic target was not a good predictor of vancomycin efficacy in MRSA experimental endocarditis.

[Surgery in the Cardiovascular Surgical Intensive Care Unit]. / Reintervenciones en una Unidad de Cuidados Intensivos de Cirugía Cardiovascular.

BACKGROUND: To analyze the indications, actions and results of the operations performed in the Cardiovascular Surgery Intensive Care Unit. METHODS: Retrospective analysis of consecutive non-selected adult patients operated in the ICU. All operations were included. Descriptive statistics were used. RESULTS: Between 2008 and 2013, 3379 consecutive adult patients were operated upon. A total of 124 operations were performed in the ICU in 109 patients, 70 male (64.2%) and 39 female (35.8%) with a mean age of 61.6 years (12-80). This represented 3.2% of all operations. During the study period, 185 patients (5.5%) were reoperated for postoperative bleeding/tamponade in the operating room. The index interventions were for valvular heart disease (34.9%), aortic disease (22.9%), ischemic heart disease (15.6%), combined valvular/ischemic (12%), valvular/aorta (11%) and miscellaneous (3.6%). The indications for reoperation were persistent bleeding 54 (43.5%), pericardial tamponade 41 (33%), low cardiac output 13 (10.5%), cardiac arrest/arrhythmia 8 (6.5%), respiratory insufficiency 6 (4.8%) and acute ischemic limb 2 (1.7%). Operations performed were: mediastinal exploration 73 (58.9%), implant/removal of ECMO 17 (13.7%), sternal closure 16 (12.9%), open resuscitation 9 (7.3%), subxyphoid drainage 7 (5.6%) and femoral embolectomy 2 (1.6%). Overall mortality was 33%. There was one case of mediastinitis (0,9%), with no difference from patients operated in the regular operating room. CONCLUSIONS: Operations in the ICU represent a safe, life-saving alternative in specific subgroups of patients. The risk of wound infection is not increased, unstable patients are not transferred and there is time savings.

Effect of vancomycin minimal inhibitory concentration on the outcome of methicillin-susceptible Staphylococcus aureus endocarditis.

BACKGROUND: Staphylococcus aureus endocarditis has a high mortality rate. Vancomycin minimum inhibitory concentration (MIC) has been shown to affect the outcome of methicillin-resistant S. aureus bacteremia, and recent data point to a similar effect on methicillin-susceptible S. aureus bacteremia. We aimed to evaluate the effect of vancomycin MIC on left-sided S. aureus infective endocarditis (IE) treated with cloxacillin. METHODS: We analyzed a prospectively collected cohort of patients with IE in a single tertiary-care hospital. Vancomycin, daptomycin, and cloxacillin MIC was determined by E-test. S. aureus strains were categorized as low vancomycin MIC (<1.5 µg/mL) and high vancomycin MIC (≥1.5 µg/mL). The primary endpoint was in-hospital mortality. RESULTS: We analyzed 93 patients with left-sided IE treated with cloxacillin, of whom 53 (57%) had a vancomycin MIC < 1.5 µg/mL and 40 (43%) a vancomycin MIC ≥ 1.5 µg/mL. In-hospital mortality was 30% (n = 16/53) in patients with a low vancomycin MIC and 53% (n = 21/40) in those with a high vancomycin MIC (P = .03). No correlation was found between oxacillin MIC and vancomycin or daptomycin MIC. Logistic regression analysis showed that higher vancomycin MIC increased in-hospital mortality 3-fold (odds ratio, 3.1; 95% confidence interval, 1.2-8.2) after adjustment for age, year of diagnosis, septic complications, and nonseptic complicated endocarditis. CONCLUSIONS: Our results indicate that vancomycin MIC could be used to identify a subgroup of patients with methicillin-susceptible S. aureus IE at risk of higher mortality. The worse outcome of staphylococcal infections with a higher vancomycin MIC cannot be explained solely by suboptimal pharmacokinetics of antibiotics.

Early in vitro and in vivo development of high-level daptomycin resistance is common in mitis group Streptococci after exposure to daptomycin.

The development of high-level daptomycin resistance (HLDR; MIC of ≥ 256 mg/liter) after exposure to daptomycin has recently been reported in viridans group streptococcus (VGS) isolates. Our study objectives were as follows: to know whether in vitro development of HLDR after exposure to daptomycin was common among clinical isolates of VGS and Streptococcus bovis; to determine whether HLDR also developed during the administration of daptomycin to treat experimental endocarditis caused by the daptomycin-susceptible, penicillin-resistant Streptococcus mitis strain S. mitis 351; and to establish whether combination with gentamicin prevented the development of HLDR in vitro and in vivo. In vitro studies were performed with 114 VGS strains (mitis group, 92; anginosus group, 10; mutans group, 8; and salivarius group, 4) and 54 Streptococcus bovis strains isolated from 168 consecutive patients with infective endocarditis diagnosed between 1995 and 2010. HLDR was only observed after 24 h of exposure to daptomycin in 27% of the mitis group, including 27% of S. mitis isolates, 47% of S. oralis isolates, and 13% of S. sanguis isolates. In our experimental model, HLDR was detected in 7/11 (63%) and 8/12 (67%) isolates recovered from vegetations after 48 h of daptomycin administered at 6 mg/kg of body weight/24 h and 10 mg/kg/24 h, respectively. In vitro, time-kill experiments showed that daptomycin plus gentamicin was bactericidal against S. mitis 351 at tested concentrations of 0.5 and 1 times the MIC and prevented the development of HLDR. In vivo, the addition of gentamicin at 1 mg/kg/8 h to both daptomycin arms prevented HLDR in 21 out of 23 (91%) rabbits. Daptomycin plus gentamicin was at least as effective as vancomycin plus gentamicin. In conclusion, HLDR develops rapidly and frequently in vitro and in vivo among mitis group streptococci. Combining daptomycin with gentamicin enhanced its activity and prevented the development of HLDR in most cases.

Clinical characteristics and outcome of infective endocarditis involving implantable cardiac devices.

CONTEXT: Infection of implantable cardiac devices is an emerging disease with significant morbidity, mortality, and health care costs. OBJECTIVES: To describe the clinical characteristics and outcome of cardiac device infective endocarditis (CDIE) with attention to its health care association and to evaluate the association between device removal during index hospitalization and outcome. DESIGN, SETTING, AND PATIENTS: Prospective cohort study using data from the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), conducted June 2000 through August 2006 in 61 centers in 28 countries. Patients were hospitalized adults with definite endocarditis as defined by modified Duke endocarditis criteria. MAIN OUTCOME MEASURES: In-hospital and 1-year mortality. RESULTS: CDIE was diagnosed in 177 (6.4% [95% CI, 5.5%-7.4%]) of a total cohort of 2760 patients with definite infective endocarditis. The clinical profile of CDIE included advanced patient age (median, 71.2 years [interquartile range, 59.8-77.6]); causation by staphylococci (62 [35.0% {95% CI, 28.0%-42.5%}] Staphylococcus aureus and 56 [31.6% {95% CI, 24.9%-39.0%}] coagulase-negative staphylococci); and a high prevalence of health care-associated infection (81 [45.8% {95% CI, 38.3%-53.4%}]). There was coexisting valve involvement in 66 (37.3% [95% CI, 30.2%-44.9%]) patients, predominantly tricuspid valve infection (43/177 [24.3%]), with associated higher mortality. In-hospital and 1-year mortality rates were 14.7% (26/177 [95% CI, 9.8%-20.8%]) and 23.2% (41/177 [95% CI, 17.2%-30.1%]), respectively. Proportional hazards regression analysis showed a survival benefit at 1 year for device removal during the initial hospitalization (28/141 patients [19.9%] who underwent device removal during the index hospitalization had died at 1 year, vs 13/34 [38.2%] who did not undergo device removal; hazard ratio, 0.42 [95% CI, 0.22-0.82]). CONCLUSIONS: Among patients with CDIE, the rate of concomitant valve infection is high, as is mortality, particularly if there is valve involvement. Early device removal is associated with improved survival at 1 year.

Forty-Year Trends in Cardiac Implantable Electronic Device Infective Endocarditis.

Background: Studies investigating cardiac implantable electronic device infective endocarditis (CIED-IE) epidemiological changes and prognosis over long periods of time are lacking. Methods: Retrospective single cardiovascular surgery center cohort study of definite CIED-IE episodes between 1981-2020. A comparative analysis of two periods (1981-2000 vs 2001-2020) was conducted to analyze changes in epidemiology and outcome over time. Results: One-hundred and thirty-eight CIED-IE episodes were diagnosed: 25 (18%) first period and 113 (82%) second. CIED-IE was 4.5 times more frequent in the second period, especially in implantable cardiac defibrillators. Age (63 [53-70] vs 71 [63-76] years, P < .01), comorbidities (CCI 3.0 [2-4] vs 4.5 [3-6], P > .01), nosocomial infections (4% vs 15.9%, P = .02) and transfers from other centers (8% vs 41.6%, P < .01) were significantly more frequent in the second period, as were methicillin-resistant coagulase-negative staphylococcal (MR-CoNS) (0% vs 13.3%, P < .01) and Enterococcus spp. (0% vs 5.3%, P = .01) infections, pulmonary embolism (0% vs 10.6%, P < .01) and heart failure (12% vs 28.3%, p < .01). Second period surgery rates were lower (96% vs 87.6%, P = .09), and there were no differences in in-hospital (20% vs 11.5%, P = .11) and one-year mortalities (24% vs 15%, P = .33), or relapses (8% vs 5.3%, P = 0.65). Multivariate analysis showed Charlson index (hazard ratios [95% confidence intervals]; 1.5 [1.16-1.94]) and septic shock (23.09 [4.57-116.67]) were associated with a worse prognosis, whereas device removal (0.11 [.02-.57]), transfers (0.13 [.02-0.95]), and second-period diagnosis (0.13 [.02-.71]) were associated with better one-year outcomes. Conclusions: CIED-IE episodes increased more than four-fold during last 40 years. Despite CIED-IE involved an older population with more comorbidities, antibiotic-resistant MR-CoNS, and complex devices, one-year survival improved.

Pulmonary artery pseudoaneurysm after Swan-Ganz catheter placement: embolization with vascular plugs.

Three patients who presented with massive hemoptysis after the insertion of a Swan-Ganz catheter for cardiac surgery are reported. Pulmonary artery pseudoaneurysms were diagnosed and successfully treated by embolization with a vascular plug. Follow-up at 15 months showed no recurrence of hemoptysis, and computed tomography helped confirm complete occlusion of the pseudoaneurysms.

Twenty-year experience with cryopreserved arterial allografts for vascular infections.

OBJECTIVES: The aim of this study was to analyse outcomes over 2 decades using cryopreserved vascular allografts to treat vascular infection. METHODS: We conducted a retrospective study of patients identified from our institutional database who were treated for primary or secondary vascular infection using implanted allografts. RESULTS: Between October 1992 and May 2014, 54 patients underwent surgery for vascular infection out of 118 patients implanted with cryopreserved vascular allografts. The 52 patients for whom we had full information form the basis of the study with a 96% follow-up. The average age was 64 ± 11 years; 87% were men; 65% had previous vascular surgery; 19% had emergency operations. A total of 75% of the patients had aortoiliofemoral infections. Five patients underwent surgery with cardiopulmonary bypass. Fifty percent required more than 1 allograft and 15% had concomitant procedures. Seventy-three percent (38/52) of specimen cultures yielded positive results with polymicrobial flora in 29%. Surgical specimens most frequently grew coagulase-negative staphylococci. The early postoperative reoperation rate was 15% for allograft-related complications. There were 20 (38%) early deaths, including deaths of acute myocardial infarction, anastomosis rupture and persistent sepsis and shock. Uncontrolled infection leading to septic shock and multiple organ failure was the cause of death in 50% of the cases. The mean duration of freedom from allograft reintervention was 12.2 years. The mean duration of freedom from allograft occlusion or limb loss was 12.1 years [95% confidence interval (CI) 9.9-14.4]. Of the 32 surviving patients, we had patency information for 66% obtained by angiography or computed tomography. The mean survival for the cohort was 5.9 years (95% CI 3.9-7.8). Mean freedom from cardiovascular infection-related death was 9.3 years (95% CI 7.2-11.4). CONCLUSIONS: Allografts can be indicated for treatment of primary/secondary infection and have remarkable results in multimorbid patients. Patients with vascular infection have a high-risk profile, around 40% mortality during the first 6 months, with reduction in overall mortality thereafter. We believe that allografts may play a role in the surgical treatment of vascular infection.

Diagnostic Accuracy of 18F-FDG PET/CT in Infective Endocarditis and Implantable Cardiac Electronic Device Infection: A Cross-Sectional Study.

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

Epidemiology and prognosis of coagulase-negative staphylococcal endocarditis: impact of vancomycin minimum inhibitory concentration.

This study describes coagulase-negative staphylococcal (CoNS) infective endocarditis (IE) epidemiology at our institution, the antibiotic susceptibility profile, and the influence of vancomycin minimum inhibitory concentration (MIC) on patient outcomes. One hundred and three adults with definite IE admitted to an 850-bed tertiary care hospital in Barcelona from 1995-2008 were prospectively included in the cohort. We observed that CoNS IE was an important cause of community-acquired and healthcare-associated IE; one-third of patients involved native valves. Staphylococcus epidermidis was the most frequent species, methicillin-resistant in 52% of patients. CoNS frozen isolates were available in 88 patients. Vancomycin MICs of 2.0 µg/mL were common; almost all cases were found among S. epidermidis isolates and did not increase over time. Eighty-five patients were treated either with cloxacillin or vancomycin: 38 patients (Group 1) were treated with cloxacillin, and 47 received vancomycin; of these 47, 27 had CoNS isolates with a vancomycin MIC <2.0 µg/mL (Group 2), 20 had isolates with a vancomycin MIC ≥ 2.0 µg/mL (Group 3). One-year mortality was 21%, 48%, and 65% in Groups 1, 2, and 3, respectively (P = 0.003). After adjusting for confounders and taking Group 2 as a reference, methicillin-susceptibility was associated with lower 1-year mortality (OR 0.12, 95% CI 0.02-0.55), and vancomycin MIC ≥ 2.0 µg/mL showed a trend to higher 1-year mortality (OR 3.7, 95% CI 0.9-15.2; P=0.069). Other independent variables associated with 1-year mortality were heart failure (OR 6.2, 95% CI 1.5-25.2) and pacemaker lead IE (OR 0.1, 95%CI 0.02-0.51). In conclusion, methicillin-resistant S.epidermidis was the leading cause of CoNS IE, and patients receiving vancomycin had higher mortality rates than those receiving cloxacillin; mortality was higher among patients having isolates with vancomycin MICs ≥ 2.0 µg/mL.

Infective endocarditis in patients with an implanted transcatheter aortic valve: Clinical characteristics and outcome of a new entity.

AIMS: This study reports one case and review the literature on TAVI-associated endocarditis (TAVIE), to describe its clinical picture and to perform an analysis on prognostic factors. METHODS AND RESULTS: A MEDLINE search from January 2002 to October 2014 revealed 31 cases of TAVIE, including 1 from our hospital. Median age was 81 years (IQR, 78-85), 53% of patients were males and the median age-adjusted Charlson score was 7 (IQR, 5-8). Heart failure was recorded in 42%, embolic events in 19%, and periannular complications in 45%. The most common causative agent was Enterococcus spp (36%). Ten patients (32%) underwent surgery and nine patients died (29%). The prognostic factors for 6-month mortality were heart failure (HR, 9.97 [3.7-24.5]; p = 0.001), periannular complications (HR, 11.82 [3.3-41.3]; p = 0.004), and nonenterococcal/streptococcal etiology (HR, 4.76 [2.1-11.1]; p = 0.03). In patients with heart failure who did not undergo surgery, mortality was 89% (8 out of 9); in those who did undergo surgery, mortality was 0% (p < 0.001). CONCLUSIONS: TAVIE is an emerging entity with high mortality. Patients with heart failure who did not undergo surgery had a higher probability of dying. Surgical treatment provided better outcomes even in patients in whom surgery had previously been ruled out.

[Predictors of lack of clinical improvement at mid-term follow-up with cardiac resynchronization therapy]. / Predictores de ausencia de mejoría clínica a medio plazo con la terapia de resincronización cardíaca.

INTRODUCTION: About 30% of all patients do not respond to cardiac resynchronization therapy for heart failure. The objective of the study was to analyze the variables that may predict the lack of response. PATIENTS AND METHOD: We analyzed the results in a series of 63 patients who received cardiac resynchronization with a biventricular device. Clinical and left ventricular function parameters were evaluated at the beginning of the study and at 6 months. Responders were defined as those who were alive, had not received a heart transplant, and who achieved more than a 10% increase in distance in the 6-minute walking test. RESULTS: Mean age was 68.3 (8) years, 51 patients (81%) were men, and NYHA functional class was III-IV in 79.4%. Mean left ventricular ejection fraction was 22.4% (6)%, QRS width was 177 (25) ms, and 77.8% were in sinus rhythm. Almost half (46%, n=29) had ischemic heart disease. At 6-month follow-up, 69.8% of the patients were responders. Ischemic heart disease, sustained monomorphic ventricular tachycardia and a degree of mitral regurgitation >II/IV before implantation were associated with lack of response. No association was found for any of the other baseline variables. Logistic regression analysis identified all three of the aforementioned variables as independent predictors of lack of response: ischemic heart disease OR=4.8, 95% CI, 1.2-18.3, P=.023; ventricular tachycardia OR=8.7, 95% CI, 1.8-41.3, P=.007; and mitral regurgitation OR=8.03, 95% CI, 1.7-37.1, P=.008. CONCLUSION: The likelihood of responding to resynchronization therapy is lower in patients with ischemic heart disease, significant mitral regurgitation, or sustained monomorphic ventricular tachycardia.

Risk factors for pericardial effusion in native valve infective endocarditis and its influence on outcome.

Data on the incidence, associated factors, and prognosis of pericardial effusion (PE) in patients with infective endocarditis (IE) are scarce. Patients with native valve IE were prospectively followed in our center from 1990 to 2007. A logistic regression analysis was performed to identify independent variables associated with PE and mortality. We included 479 episodes of IE from 459 patients (70% men, mean age 51 years). Small-to-moderate PE was observed in 109 episodes (23%) and large-to-very large PE was observed in 9 episodes (2%). Patients with small-to-moderate PE had a greater prevalence of intravenous drug use (38% vs 23%) and more frequent right-sided IE than patients without PE (33% vs 17%). Patients with large-to-very large PE had a higher rate of systemic emboli (22% vs 18%) and periannular abscess (22% vs 6%) than patients without PE. Renal failure was associated with a higher risk of PE (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.3 to 3.3); age was associated with a lower risk of PE (OR 0.98, 95% CI 0.97 to 0.99). One-year mortality of patients with IE with large-to-very large PE was higher than that of patients with small-to-moderate and absence of PE (56%, 18%, and 24%, respectively, p = 0.033). Large-to-very large PE increases the 1-year mortality of IE (OR 3.0, 95% CI 1.2 to 7.9). In conclusion, renal failure and younger age are associated with a higher risk of PE. Large-to-very large PE was associated with an increase in 1-year mortality.

Retrieval of scrap metal from an abdominal aortic aneurysm during the follow-up.

A 75-year-old patient underwent open repair of a rapidly expanded aneurysm after previous multiple endovascular repair (EVAR) attempts by others. Open surgical reconstruction allowed the explants of all metallic components of implanted stent-grafts. This is still an uncommon phenomenon due to the still low late reintervention rate.

Erosion of lumbar vertebral bodies by an anastomotic false aneurysm late after implantation of a prosthetic aortic bifurcated graft.

False aneurysms are seen at any anastomotic level. Erosion of surrounding structures is a rare event that needs surgical treatment. The case of a patient with proximal Dacron bifurcated graft false aneurysm eroding lumbar vertebral bodies is presented. This is an uncommon but very serious complication from aortic grafts.

An unusual travel of an endocardial pacing lead to the left ventricle.

A 80-year-old lady was admitted because of dyspnea, complete AV block and ventricular rate of 15 bpm. A DDDR pacemaker was successfully implanted. Postoperative EKG showed right bundle branch block and X-ray the ventricular lead in the left ventricle. It traveled all the way through a foramen ovale being later relocated in the right apex.