Outcome of Enterococcus faecalis infective endocardits according to the length of antibiotic therapy: Prelininary data from a cohort of 78 patients.

Background International guidelines recommend 4 weeks of treatment with ampicillin plus gentamicin (A+G) for uncomplicated native valve Enterococcus faecalis infective endocarditis (EFIE) and 6 weeks in the remaining cases. Ampicillin plus ceftriaxone (A+C) is always recommended for at least 6w, with no available studies assessing its suitability for 4w. We aimed to investigate differences in the outcome of EFIE according to the duration (4 versus 6 weeks) of antibiotic treatment (A+G or A+C). Methods Retrospective analysis from a prospectively collected cohort of 78 EFIE patients treated with either A+G or A+C. Results 32 cases (41%) were treated with A+G (9 for 4w, 28%) and 46 (59%) with A+C (14 for 4w, 30%). No significant differences were found in 1-year mortality according to the type of treatment (31% and 24% in A+G and A+C, respectively; P = 0.646) or duration (26% and 27% at 4 and 6w, respectively; P = 0.863). Relapses were more frequent among survivors treated for 4w than in those treated for 6w (3/18 [17%] at 4w and 1/41 [2%] at 6w; P = 0.045). Three out of 4 (75%) relapses occurred in cirrhotic patients. Conclusions A 4-week course of antibiotic treatment might not be suitable neither for A+G nor A+C for treating uncomplicated native valve EFIE

HACEK infective endocarditis: epidemiology, clinical features outcome: A case-control study

OBJECTIVES: The study aimed to describe the epidemiology, microbiological and clinical features of a population sample of 17 patients with HACEK-IE and to compare them with matched control patients with IE caused by Viridans group Streptococci (VGS-IE). METHODS: Description of definite (14; 82.2%) and possible (3; 17.6%) HACEK-IE included in the 'Infective Endocarditis Hospital Clínic of Barcelona' (IE-HCB) database between 1979 and 2016. Furthermore, a retrospective case-control analysis was performed, matching each case to three VGS-IE controls registered in the same database during the same period of time. RESULTS: Seventeen out of 1,209 IE cases (1.3%, 95%CI 0.69-1.91) were due to HACEK group. The most frequent isolated HACEK species were Aggregatibacter spp (11; 64.7%). Intracardiac vegetations were present in 70.6% of cases. Left heart failure (LHF) was present in 29.4% of cases. Ten patients (58.8%) required in-hospital surgery and none died during hospitalization. In the case-control analysis, there was a trend toward larger vegetations in the HACEK-IE group (median (IRQ) size=11.5 (10.0-20.0) mm vs 9.0 (7.0-13.0) mm; p=0.068). Clinical manifestations, echocardiographic findings, LHF rate, systemic emboli and other complications were all comparable (p >0.05). In-hospital surgery and mortality were similar for both groups. One-year mortality was lower for HACEK-IE (1/17 vs. to 6/48, p=0.006). CONCLUSIONS: HACEK-IE represented 1.3% of all IE cases. Clinical features and outcome were comparable with the VGS-IE control group. Despite the trend to

Influence of Vancomycin Minimum Inhibitory Concentration on the Outcome of Methicillin-Susceptible Staphylococcus aureus Left-Sided Infective Endocarditis Treated with Anti-staphylococcal Beta-Lactam Antibiotics; a Prospective Cohort Study by the International Collaboration on Endocarditis

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

Effectiveness of vancomycin plus cloxacillin compared with vancomycin, cloxacillin and daptomycin single therapies in the treatment of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in a rabbit model of experimental endocarditis

Objectives: To investigate if the addition of cloxacillin to vancomycin enhances the activity of both monotherapies for treating MSSA and MRSA experimental endocarditis (EE) in rabbits. Methods: Vancomycin plus cloxacillin was compared with the respective monotherapies and daptomycin. In vitro time-kill studies were performed using standard (105 cfu) and high (108 cfu) inocula of five MRSA, one glycopeptide-intermediate (GISA) and five MSSA strains. One MSSA (MSSA-678) and one MRSA (MRSA-277) strain were selected to be used in the in vivo model. A human-like pharmacokinetics model was applied and the equivalents of cloxacillin 2 g/4 h IV and daptomycin 6 mg/kg/day IV were administered. To optimize vancomycin activity, dosage was adjusted to achieve an AUC/MIC ≥400. Results: Daptomycin sterilized significantly more vegetations than cloxacillin (13/13, 100% versus 9/15, 60%; P = 0.02) and showed a trend of better activity than vancomycin (10/14, 71%; P = 0.09) and vancomycin plus cloxacillin (10/14, 71%; P = 0.09) against MSSA-678. Addition of cloxacillin to vancomycin (13/15, 87%) was significantly more effective than vancomycin (8/16, 50%; P = 0.05) and showed similar activity to daptomycin (13/18, 72%; P = 0.6) against MRSA-277. In all treatment arms, the bacterial isolates recovered from vegetations were re-tested and showed the same daptomycin susceptibility as the original strains. Conclusions: Vancomycin plus cloxacillin proved synergistic and bactericidal activity against MRSA. Daptomycin was the most efficacious option against MSSA and similar to vancomycin plus cloxacillin against MRSA. In settings with high MRSA prevalence, vancomycin plus cloxacillin might be a good alternative for empirical therapy of S. aureus IE

The Combination of Daptomycin plus Fosfomycin has Synergistic, Potent and Rapid Bactericidal Activity against Methicillin-ResistantStaphylococcus aureus(MRSA) in a Rabbit Model of Experimental Endocarditis (EE).

This study aims to investigate whether the addition of fosfomycin or cloxacillin to daptomycin provides better outcomes in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) experimental aortic endocarditis in rabbits. Five MRSA strains were used to perform in vitro time-kill studies at standard (105) and high (108) inocula. Combined therapy was compared with daptomycin monotherapy treatment in the MRSA experimental endocarditis model. A human-like pharmacokinetics model was applied and the equivalents of cloxacillin 2g/4hiv, fosfomycin 2g/6h iv and daptomycin 6-10mg/kg/d iv were administered. The combination of daptomycin and fosfomycin or cloxacillin was synergistic in the five strains tested at both inocula. A bactericidal effect was detected in four out of five strains tested with both combinations. The MRSA-277 strain (vancomycin MIC, 2 mcg/mL) was used for the experimental endocarditis model. Daptomycin plus fosfomycin significantly improved the efficacy of daptomycin monotherapy at 6 mg/kg/d in terms of both the proportion of sterile vegetations (100% vs. 72%, P=.046) and the decrease in the density of bacteria within the vegetations (P=.025). Daptomycin plus fosfomycin was as effective as daptomycin monotherapy at 10 mg/kg/d (100% vs. 93%, P=1.00) and had similar activity to daptomycin plus cloxacillin when daptomycin was administered at 6 mg/kg/d (100% vs. 88%, P=0.48). Daptomycin non-susceptibility was not detected in any of the isolates recovered from vegetations. In conclusion, for the treatment of MRSA experimental endocarditis, the combination of daptomycin plus fosfomycin showed synergistic and bactericidal activity.Copyright © 2018 American Society for Microbiology

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

One-year outcome following biological or mechanical valve replacement for infective endocarditis

Background: Nearly half of patients require cardiac surgery during the acute phase of infective endocarditis (IE). We describe the characteristics of patients according to the type of valve replacement (mechanical or biological), and examine whether the type of prosthesis was associated with in-hospital and 1-year mortality. Methods and results: Among 5591 patients included in the International Collaboration on Endocarditis Prospective Cohort Study, 1467 patients with definite IE were operated on during the active phase and had a biological (37%) or mechanical (63%) valve replacement. Patients who received bioprostheses were older (62 vs 54 years), more often had a history of cancer (9% vs 6%), and had moderate or severe renal disease (9% vs 4%); proportion of health care-associated IE was higher (26% vs 17%); intracardiac abscesses were more frequent (30% vs 23%). In-hospital and 1-year death rates were higher in the bioprosthesis group, 20.5% vs 14.0% (p = 0.0009) and 25.3% vs 16.6% (p < .0001), respectively. In multivariable analysis, mechanical prostheses were less commonly implanted in older patients (odds ratio: 0.64 for every 10 years), and in patients with a history of cancer (0.72), but were more commonly implanted in mitral position (1.60). Bioprosthesis was independently associated with 1-year mortality (hazard ratio: 1.298). Conclusions: Patients with IE who receive a biological valve replacement have significant differences in clinical characteristics compared to patients who receive a mechanical prosthesis. Biological valve replacement is independently associated with a higher in-hospital and 1-year mortality, a result which is possibly related to patient characteristics rather than valve dysfunction

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Efficacy and safety of fosfomycin plus imipenem versus vancomycin for complicated bacteraemia and endocarditis due to methicillin-resistant Staphylococcus aureus: a randomized clinical trial

FOSIMI Investigators.This work was supported by the Ministerio de Sanidad y Consumo of Spain (Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Madrid, Spain, Grant #EC0800190). JMP received a “Rio Hortega” Research Grant (CM14/00135; 2015-16) from Instituto de Salud Carlos III and the Ministerio de Economia and Competitividad, Madrid (Spain) and the ESCMID/FEMS Research Fellowship 2016. JMM received a personal 80:20 research grant from the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017–19

Daptomycin Is Effective in Treatment of Experimental Endocarditis Due to Methicillin-Resistant and Glycopeptide-Intermediate Staphylococcus aureus▿

Daptomycin is a lipopeptide antibiotic with potent in vitro activity against gram-positive cocci, including Staphylococcus aureus. This study evaluated the in vitro and in vivo efficacies of daptomycin against two clinical isolates: methicillin-resistant S. aureus (MRSA) 277 (vancomycin MIC, 2 μg/ml) and glycopeptide-intermediate S. aureus (GISA) ATCC 700788 (vancomycin MIC, 8 μg/ml). Time-kill experiments demonstrated that daptomycin was bactericidal in vitro against these two strains. The in vivo activity of daptomycin (6 mg/kg of body weight every 24 h) was evaluated by using a rabbit model of infective endocarditis and was compared with the activities of a high-dose (HD) vancomycin regimen (1 g intravenously every 6 h), the recommended dose (RD) of vancomycin regimen (1 g intravenously every 12 h) for 48 h, and no treatment (as a control). Daptomycin was significantly more effective than the vancomycin RD in reducing the density of bacteria in the vegetations for the MRSA strains (0 [interquartile range, 0 to 1.5] versus 2 [interquartile range, 0 to 5.6] log CFU/g vegetation; P = 0.02) and GISA strains (2 [interquartile range, 0 to 2] versus 6.6 [interquartile range, 2.0 to 6.9] log CFU/g vegetation; P < 0.01) studied. In addition, daptomycin sterilized more MRSA vegetations than the vancomycin RD (13/18 [72%] versus 7/20 [35%]; P = 0.02) and sterilized more GISA vegetations than either vancomycin regimen (12/19 [63%] versus 4/20 [20%]; P < 0.01). No statistically significant difference between the vancomycin HD and the vancomycin RD for MRSA treatment was noted. These results support the use of daptomycin for the treatment of aortic valve endocarditis caused by GISA and MRSA