Juan C. Paré

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.

Correlation between silent cerebral white matter lesions and left ventricular mass and geometry in essential hypertension

BACKGROUND It has been proposed that concentric left ventricular hypertrophy (LVH) is related to a worse degree of target organ damage in hypertensives with this feature than in those without. Moreover, the presence of cerebral white matter lesions (WMLs) is considered to be an early marker of brain damage in essential hypertension. The aim of this study was to assess the association between the presence of silent WMLs and left ventricular mass and geometry in middle-aged individuals with hypertension that had never been treated. METHODS A total of 62 patients (39 men, 23 women, aged 50 to 60 years, mean age 54.4 +/- 3.2 years) with never-treated essential hypertension and without clinical evidence of target organ damage were studied. All patients underwent brain magnetic resonance imaging and were classified into two groups according to the presence or absence of WMLs. Echocardiography measuring posterior wall thickness (PWT), interventricular septum thickness (IVST) and left ventricular end-diastolic diameter (LVEDD) was also performed. Left ventricular mass index (LVMI) was calculated using the Penn convention criteria, and relative wall thickness ratio (RWT) was estimated by the standard formula: 2 x PWT/LVEDD. RESULTS Hypertensive patients with WMLs exhibited significantly higher PWT, IVST, LVMI, and RWT when compared with hypertensive patients without WMLs. In addition, 23 of 26 hypertensive patients with WMLs showed echocardiographic criteria for LVH that was significantly higher than that observed in hypertensive patients without WMLs (21 of 36; P = .01). Concentric hypertrophy (LVH and RWT > or = 0.45) was present in 14 hypertensive patients with WMLs and in only four patients without WMLs (P = .002). CONCLUSION There is a close association between cerebral WMLs and concentric LVH in asymptomatic middle-aged hypertensive patients, independent of blood pressure values.

Native Valve Endocarditis due to Candida glabrata Treated without Valvular Replacement: A Potential Role for Caspofungin in the Induction and Maintenance Treatment

Conventional antifungal therapy for fungal endocarditis has been associated with a poor cure rate. Therefore, combined medical and surgical therapy has been recommended. However, new potent antifungal agents, such as echinocandins, could increase the medical options and, in some cases, avoid the need for surgery. We report a case of Candida endocarditis treated successfully without valve replacement with intravenous liposomal amphotericin B (total dose, 4 g) and intravenous caspofungin (a 100-mg loading dose followed by 50 mg per day for 8 weeks) as induction therapy and intravenous caspofungin (100 mg 3 times per week for 12 weeks) as maintenance therapy.

Efficacy and Safety of Fosfomycin Plus Imipenem as Rescue Therapy for Complicated Bacteremia and Endocarditis Due to Methicillin-Resistant Staphylococcus aureus: A Multicenter Clinical Trial

BACKGROUND There is an urgent need for alternative rescue therapies in invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We assessed the clinical efficacy and safety of the combination of fosfomycin and imipenem as rescue therapy for MRSA infective endocarditis and complicated bacteremia. METHODS The trial was conducted between 2001 and 2010 in 3 Spanish hospitals. Adult patients with complicated MRSA bacteremia or endocarditis requiring rescue therapy were eligible for the study. Treatment with fosfomycin (2 g/6 hours IV) plus imipenem (1 g/6 hours IV) was started and monitored. The primary efficacy endpoints were percentage of sterile blood cultures at 72 hours and clinical success rate assessed at the test-of-cure visit (45 days after the end of therapy). RESULTS The combination was administered in 12 patients with endocarditis, 2 with vascular graft infection, and 2 with complicated bacteremia. Therapy had previously failed with vancomycin in 9 patients, daptomycin in 2, and sequential antibiotics in 5. Blood cultures were negative 72 hours after the first dose of the combination in all cases. The success rate was 69%, and only 1 of 5 deaths was related to the MRSA infection. Although the combination was safe in most patients (94%), a patient with liver cirrhosis died of multiorgan failure secondary to sodium overload. There were no episodes of breakthrough bacteremia or relapse. CONCLUSIONS Fosfomycin plus imipenem was an effective and safe combination when used as rescue therapy for complicated MRSA bloodstream infections and deserves further clinical evaluation as initial therapy in these infections.

Lack of association between ACE gene polymorphism and left ventricular hypertrophy in essential hypertension.

The possible association between the insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme (ACE) gene and left ventricular hypertrophy (LVH) was investigated in a group of essential hypertensive patients. Seventy-one essential hypertensive patients (35 men and 36 women), aged 51 ± 1 years, were genotyped by PCR for the I/D polymorphism of the ACE gene. Cardiac morphology and function were assessed by means of M-mode echocardiography. The relative frequencies of the three genotypes, DD, DI, and II, were respectively: 24%, 55%, and 21%. Mean values of left ventricular mass index were 145, 144, and 150 g/m2 for DD, DI, and II genotypes, without significant differences among them (P = 0.82). Likewise, the prevalence of LVH (76%, 64%, and 87%) was not significantly different among the three genotypes (P = 0.23). We conclude that the ACE gene I/D polymorphism is not associated with LVH in essential hypertension.

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.

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.

Epidemiology, Clinical Features, and Outcome of Infective Endocarditis due to Abiotrophia Species and Granulicatella Species: Report of 76 Cases, 2000–2015

Background Infective endocarditis (IE) caused by Abiotrophia (ABI) and Granulicatella (GRA) species is poorly studied. This work aims to describe and compare the main features of ABI and GRA IE. Methods We performed a retrospective study of 12 IE institutional cases of GRA or ABI and of 64 cases published in the literature (overall, 38 ABI and 38 GRA IE cases). Results ABI/GRA IE represented 1.51% of IE cases in our institution between 2000 and 2015, compared to 0.88% of HACEK (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella)-related IE and 16.62% of Viridans group streptococci (VGS) IE. Institutional ABI/GRA IE case characteristics were comparable to that of VGS, but periannular complications were more frequent (P = .008). Congenital heart disease was reported in 4 (10.5%) ABI and in 11 (28.9%) GRA cases (P = .04). Mitral valve was more frequently involved in ABI than in GRA (P < .001). Patient sex, prosthetic IE, aortic involvement, penicillin susceptibility, and surgical treatment were comparable between the genera. New-onset heart failure was the most frequent complication without genera differences (P = .21). Five (13.2%) ABI patients and 2 (5.3%) GRA patients died (P = .23). Factors associated with higher mortality were age (P = .02) and new-onset heart failure (P = .02). The genus (GRA vs ABI) was not associated with higher mortality (P = .23). Conclusions GRA/ABI IE was more prevalent than HACEK IE and approximately one-tenth as prevalent as VGS; periannular complications were more frequent. GRA and ABI genera IE presented similar clinical features and outcomes. Overall mortality was low, and related to age and development of heart failure.

Relation of Left Ventricular Hypertrophy to Regional Cerebral Blood Flow: Single Photon Emission Computed Tomography Abnormalities in Essential Hypertension

Several reports have shown that left ventricular hypertrophy (LVH) is an independent predictor of acute cerebrovascular events. The aim of the present study was to investigate the relationship between LVH and cerebral blood flow in middle‐aged patients with essential hypertension. Forty never‐treated hypertensive patients (24 men, 16 women, aged 50–60 years) without clinical evidence of target organ damage were studied. Regional cerebral blood flow was measured by means of single photon emission computed tomography of the brain. Twenty‐nine patients showed echocardiographic criteria of LVH; 11 patients did not show this feature. No differences were found in regional cerebral blood flow ratio of all brain areas studied between hypertensives with or without LVH except for the striatum area. The regional cerebral blood flow ratio was significantly reduced in the striatum region of hypertensive patients with LVH, compared with patients without LVH (91.5±7.4 vs 98.1±8.3; P=.023). This relationship remained significant after adjusting for blood pressure. The authors conclude that the presence of LVH in middle‐aged patients with essential hypertension is associated with a reduction of regional cerebral blood flow in the striatum area.

Relationship Between Enterococcus faecalis Infective Endocarditis and Colorectal Neoplasm: Preliminary Results From a Cohort of 154 Patients.

INTRODUCTION AND OBJECTIVES The association between Streptococcus bovis group infective endocarditis and colorectal neoplasm (CRN) is well-known. However, no studies have assessed the association between Enterococcus faecalis infective endocarditis (EFIE) and CRN. We aimed to determine whether the prevalence of CRN is higher in patients with EFIE and an unclear source of infection than in patients with EFIE and a known source of infection or in the general population. METHODS Retrospective analysis of a cohort of 154 patients with definite EFIE (109 with an unclear source of infection and 45 with an identified source) from 2 Spanish teaching hospitals to determine the prevalence of CRN and other colorectal diseases. RESULTS In the group with an unknown source of infection, 61 patients (56%) underwent colonoscopy; of these, 31 (50.8%) had CRN. Nonadvanced colorectal adenoma was detected in 22 patients (36%), advanced adenoma in 5 (8.2%), and colorectal carcinoma (CRC) in 4 (6.6%). Among patients who survived the EFIE episode with ≥ 2 years of follow-up, 1 case of CRC was subsequently diagnosed. Only 6 patients (13.3%) with an identified focus of infection underwent colonoscopy; 1 of these patients (16.7%) was diagnosed with CRN. The prevalence of adenomas was slightly higher than that of the Spanish population in the same age range, whereas that of CRC was 17-fold higher. CONCLUSIONS CRN was found in more than half of patients with EFIE and an unclear focus of infection who underwent colonoscopy. Colonoscopy should be recommended in patients with EFIE and an unclear source of infection.