Evaluation of penicillin-gentamicin and dual beta-lactam therapies in Enterococcus faecalis infective endocarditis

Author(s):  
Lauren Freeman ◽  
Ashley Milkovits ◽  
Lauren McDaniel ◽  
Nathan Everson
2019 ◽  
Vol 15 (4) ◽  
pp. 586-592
Author(s):  
E. V. Shikh ◽  
T. E. Morozova ◽  
V. N. Drozdov ◽  
N. B. Lazareva ◽  
D. A. Shatsky ◽  
...  

The frequency of infective endocarditis (IE) has increased 3 times over the past 30 years. The incidence of IE morbidity is recorded in all countries of the world and in the Russian Federation more than 40 people per 1 million population get sick. One of the most frequent causative agents of infective endocarditis is Enterococcus faecalis (E. faecalis), which takes the third place in the structure of the frequency of IE pathogens. Enterococcal IE remains a disease with high mortality, despite the emergence of new groups of antibacterial drugs. This review includes the results of studies of the efficacy and safety of various antimicrobial regimens of IE caused by E. faecalis. The analysis of data from foreign and native studies of antimicrobial treatment in patients with infective endocarditis, accompanied by enterococcal bacteremia is presented in the review. The search for literature performed by using medical databases: MEDLINE, EMBASE, eLIBRARY. The current review included studies of the efficacy and safety of antimicrobial treatment. The main antibiotic therapy regimens of IE caused by E. faecalis include 2 beta-lactam antibiotics or a combination of ampicillin and gentamicin, according to the results of 5 found studies. Found antimicrobial regimens significantly did not affect mortality. Data from international registries testify to the efficacy and safety of daptomycin monotherapy for enterococcal endocarditis. Linezolid and daptomycin are the main drugs of treating infective endocarditis caused by vancomycin-resistant enterococci. Native studies report of a high level of resistance of enterococcal strains to beta-lactam antibacterial drugs. The duration of fever, the frequency of surgical heart valves interventions, the duration of bacteremia are not fully represented in each of the studies, and it is difficult to evaluate these factors. Ampicillin+ceftriaxone and ampicillin+gentamicin are the main antimicrobial treatment regimens of enterococcal endocarditis. Efficacy of these regimens is not significantly different. Treatment of IE should be carried out taking into the epidemiological situation and the strain resistance.


2016 ◽  
Vol 3 (suppl_1) ◽  
Author(s):  
Abdelghani El Rafei ◽  
Daniel C. Desimone ◽  
Muhammad R. Sohail ◽  
James Steckelberg ◽  
Walter R. Wilson ◽  
...  

2021 ◽  
Author(s):  
Kevin J Westbrook ◽  
Gayatri Shankar Chilambi ◽  
Hayley R Nordstrom ◽  
Alina Iovleva ◽  
Niyati H Shah ◽  
...  

Enterococcus faecalis is a leading cause of infective endocarditis (IE), especially among older patients with comorbidities. Here we investigated the genomic diversity and antimicrobial susceptibility of 33 contemporary E. faecalis isolates from definite or probable IE cases at the University of Pittsburgh Medical Center (UPMC) between 2018 and 2020. Isolates belonging to two multi-locus sequence types (STs), ST6 and ST179, were isolated from nearly 40% of IE patients. Both of these dominant STs carried known beta-lactam resistance-associated mutations affecting the low-affinity penicillin-binding protein 4 (PBP4). We assessed the ability of ampicillin and ceftriaxone (AC) both alone and in combination to inhibit genetically diverse E. faecalis IE isolates in checkerboard synergy assays and an in vitro one-compartment pharmacokinetic-pharmacodynamic (PK-PD) model of AC treatment. ST6 isolates as well as an isolate with a mutation in the PP2C-type protein phosphatase IreP had higher ceftriaxone MICs compared to other isolates, and showed diminished in vitro synergy of AC. Additionally, both ST6 and ST179 isolates exhibited regrowth after 48 hours of humanized exposures to AC. Overall, we found evidence for diminished in vitro AC activity among E. faecalis IE isolates with PBP4 and IreP mutations. This study highlights the need to evaluate alternate antibiotic combinations in clinical practice against diverse contemporary E. faecalis IE isolates.


2020 ◽  
Vol 02 ◽  
Author(s):  
Masood Ghori ◽  
Nadya O. Al Matrooshi ◽  
Samir Al Jabbari ◽  
Ahmed Bafadel ◽  
Gopal Bhatnagar

: Infective Endocarditis (IE), a known complication of hemodialysis (HD), has recently been categorized as Healthcare-Associated Infective Endocarditis (HAIE). Single pathogen bacteremia is common, polymicrobial endocardial infection is rare in this cohort of the patients. We report a case of endocarditis caused by Enterococcus faecalis (E. faecalis) and Burkholderia cepacia (B. cepacia), a first ever reported combination of a usual and an unusual organism, respectively, in a patient on HD. Clinical presentation of the patient, its complicated course ,medical and surgical management ,along with microbial and echocardiographic findings is presented herein. The authors believe that presentation of this case of HAIE may benefit and contribute positively to cardiac science owing to the rare encounter of this organism as a pathogen in infective endocarditis and the difficulties in treating it.


IDCases ◽  
2021 ◽  
Vol 24 ◽  
pp. e01082
Author(s):  
S. Khan ◽  
C. Urban ◽  
V. Singh ◽  
D. Liu ◽  
S. Segal-Maurer ◽  
...  

2018 ◽  
Vol 76 (8) ◽  
Author(s):  
Kavindra V Singh ◽  
Kenneth L Pinkston ◽  
Peng Gao ◽  
Barrett R Harvey ◽  
Barbara E Murray

AbstractAce (Adhesin to collagen from Enterococcus faecalis) is a cell-wall anchored protein that is expressed conditionally and is important for virulence in a rat infective endocarditis (IE) model. Previously, we showed that rats immunized with the collagen binding domain of Ace (domain A), or administered anti-Ace domain A polyclonal antibody, were less susceptible to E. faecalis endocarditis than sham-immunized controls. In this work, we demonstrated that a sub nanomolar monoclonal antibody (mAb), anti-Ace mAb70, significantly diminished E. faecalis binding to ECM collagen IV in in vitro adherence assays and that, in the endocarditis model, anti-Ace mAb70 pre-treatment significantly reduced E. faecalis infection of aortic valves. The effectiveness of anti-Ace mAb against IE in the rat model suggests it might serve as a beneficial agent for passive protection against E. faecalis infections.


PLoS ONE ◽  
2018 ◽  
Vol 13 (4) ◽  
pp. e0196317 ◽  
Author(s):  
Juan M. Pericàs ◽  
Carlos Cervera ◽  
Asunción Moreno ◽  
Cristina Garcia-de-la-Mària ◽  
Manel Almela ◽  
...  

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 817-818
Author(s):  
B. Hugues ◽  
B. Emsen ◽  
J. Ternacle ◽  
R. Huguet ◽  
A. Fiore ◽  
...  

Background:Five to eleven percent of infective endocarditis (IE) are associated with a musculoskeletal infection. Thanks to its good sensitivity, the use of PET-CT in this pathology makes it possible to confirm the diagnosis by seeking valvular hypermetabolism but also by mapping distant septic foci.Objectives:The main objective of our study was to assess the prevalence of osteoarticular fixation (OAF) with PET-CT, symptomatic or not, in patients with IE. The secondary objectives were to determine predictive factors for osteoarticular infections such as the type of valve damage (native or prosthetic) and germ.Methods:This study was carried out on the basis of a prospective cohort of patients admitted in the department of cardiology in Henri Mondor Hospital for IE suspicion between August 2015 and July 2019. Demographic, clinical, bacteriological, imaging and therapeutic data have been collected. Patients matching Duke’s modified criteria according to ESC 2015 (Duke + IE) and / or a cardiac fixation according to standard whole-body PET-CT were included in the analysis. All of the PET-CT scans were reviewed by a nuclear medicine specialist to confirm whether or not there was a heart condition and to look for septic-looking OAF.Results:From this cohort, we included 90 IE Duke + patients and 42 patients with cardiac PET-CT fixation (including 31 IE Duke +). In the IE Duke + group, we found OAF in 18 patients (20%), 39% of whom were asymptomatic. There were 9 spondylodiscitis (4 on the cervical level, 7 on the thoracic level, and 2 on the lumbar level), 5 glenohumeral arthritis, 2 coxofemoral arthritis, 1 sternoclavicular arthritis and 1 sacroiliac arthritis. The IE affected the aortic valve in 50% of the cases and the mitral valve in 22%. In other cases, the infection involved the internal automatic defibrillator (ICD) or the pacemaker. The valves were prosthetic in 73% of the cases. The bacterial ecology was mainly represented by Enterococcus faecalis (39%) then staphylococcus aureus (17%) against 14% and 13% respectively in the entire IE Duke + group. In the group with cardiac PET-CT fixation, OAF was found in 10 patients (40%), 70% of whom were asymptomatic. Among them, there were 5 spondylodiscitis (2 cervico- thoracic and 3 exclusively thoracic), 2 glenohumeral arthritis (20%), 2 coxofemoral arthritis and 1 sternoclavicular arthritis. The IE affected the aortic valve in 60% of the cases, mitral in 30% of the cases and it was an infection on ICD in 10% of the cases. The main germs found were Enterococcus faecalis (30% of cases) and Staphylococcus epidermidis (20% of cases).Conclusion:In patients with IE, PET-CT seems to be interesting in detection of osteoarticular infections, and consequently, could impact the diagnosis and the treatment modalities. In our cohort, 1 patient in 5 had an OAF and nearly 40% of them were asymptomatic. The overrepresentation of enterococcus is consistent with recent data in the literatureReferences:[1]Dahl A, Iversen K, Tonder N, Hoest N, Arpi M, Dalsgaard M, et al. Prevalence of Infective Endocarditis in Enterococcus faecalis Bacteremia. J Am Coll Cardiol. 16 juill 2019;74(2):193‑201.Disclosure of Interests:Benjamin HUGUES: None declared, Bérivan EMSEN: None declared, Julien TERNACLE: None declared, Raphaëlle HUGUET: None declared, Antonio FIORE: None declared, Raphaëlle LEPEULE: None declared, Xavier Chevalier: None declared, Mukedaisi ABULIZI: None declared, Florent Eymard Consultant of: Regenlab


2020 ◽  
Vol 65 (1) ◽  
pp. e02099-20
Author(s):  
Laura Herrera-Hidalgo ◽  
Arístides de Alarcón ◽  
Luis Eduardo López-Cortes ◽  
Rafael Luque-Márquez ◽  
Luis Fernando López-Cortes ◽  
...  

ABSTRACTCeftriaxone administered as once-daily high-dose short infusion combined with ampicillin has been proposed for the treatment of Enterococcus faecalis infective endocarditis in outpatient parenteral antibiotic therapy programs (OPAT). This combination requires synergistic activity, but the attainment of ceftriaxone synergic concentration (Cs) with the regimen proposed for OPAT has not been studied. This phase II pharmacokinetic study enrolled healthy adult volunteers who underwent two sequential treatment phases. During phase A, volunteers received 2 g of ceftriaxone each 12 h during 24 h followed by a 7-day wash-out. Then the participants received phase B, which consisted of a single dose of 4 g of ceftriaxone. Throughout both phases, each volunteer underwent intensive pharmacokinetic (PK) sampling over 24 h. Ceftriaxone total and unbound concentrations were measured. Twelve participants were enrolled and completed both phases. Mean ceftriaxone total and free concentrations 24 h after the administration of 2 g each 12 h were 86.44 ± 25.90 mg/liter and 3.59 ± 1.35 mg/liter, respectively, and after the 4-g single dose were 34.60 ± 11.16 mg/liter and 1.40 ± 0.62 mg/liter, respectively. Only 3 (25%) patients in phase A maintained unbound plasma concentrations superior to the suggested Cs = 5 mg/liter during 24 h, and none (0%) in phase B. No grade 3 to 4 adverse events or laboratory abnormalities were observed. Ceftriaxone optimal exposure combined with ampicillin to achieve maximal synergistic activity against E. faecalis required for the treatment of infective endocarditis remains unknown. However, the administration of a single daily dose of 4 g of ceftriaxone implies a reduction in the time of exposure to the proposed Cs. (This study has been registered in the European Union Drug Regulating Authorities Clinical Trials [EudraCT] database under identifier 2017-003127-29.)


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