scholarly journals Anti-biofilm Approach in Infective Endocarditis Exposes New Treatment Strategies for Improved Outcome

2021 ◽  
Vol 9 ◽  
Author(s):  
Christian Johann Lerche ◽  
Franziska Schwartz ◽  
Marie Theut ◽  
Emil Loldrup Fosbøl ◽  
Kasper Iversen ◽  
...  
Keyword(s):  
Infective Endocarditis ◽  
Antibiotic Therapy ◽  
Biofilm Formation ◽  
Heart Valves ◽  
Treatment Strategies ◽  
High Dose ◽  
Special Focus ◽  
Infective Disease ◽  
New Treatment ◽  
Improved Outcome

Infective endocarditis (IE) is a life-threatening infective disease with increasing incidence worldwide. From early on, in the antibiotic era, it was recognized that high-dose and long-term antibiotic therapy was correlated to improved outcome. In addition, for several of the common microbial IE etiologies, the use of combination antibiotic therapy further improves outcome. IE vegetations on affected heart valves from patients and experimental animal models resemble biofilm infections. Besides the recalcitrant nature of IE, the microorganisms often present in an aggregated form, and gradients of bacterial activity in the vegetations can be observed. Even after appropriate antibiotic therapy, such microbial formations can often be identified in surgically removed, infected heart valves. Therefore, persistent or recurrent cases of IE, after apparent initial infection control, can be related to biofilm formation in the heart valve vegetations. On this background, the present review will describe potentially novel non-antibiotic, antimicrobial approaches in IE, with special focus on anti-thrombotic strategies and hyperbaric oxygen therapy targeting the biofilm formation of the infected heart valves caused by Staphylococcus aureus. The format is translational from preclinical models to actual clinical treatment strategies.

scholarly journals Is Once-Daily High-Dose Ceftriaxone plus Ampicillin an Alternative for Enterococcus faecalis Infective Endocarditis in Outpatient Parenteral Antibiotic Therapy Programs?

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 ◽  
...  
Keyword(s):  
Single Dose ◽  
Infective Endocarditis ◽  
Antibiotic Therapy ◽  
Enterococcus Faecalis ◽  
High Dose ◽  
Synergistic Activity ◽  
Parenteral Antibiotic ◽  
Once Daily ◽  
Content Type ◽  
Outpatient Parenteral Antibiotic Therapy

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.)

Seeing is believing: Can biofilm diagnostics guide individualized therapy in endocarditis?

2020 ◽  
Author(s):  
Judith Kikhney ◽  
Laura Kursawe ◽  
Swb Eichinger ◽  
Walter Eichinger ◽  
Julia Schmidt ◽  
...  
Keyword(s):  
Antibiotic Therapy ◽  
Biofilm Formation ◽  
Heart Valves ◽  
Single Cells ◽  
Intergenic Spacer ◽  
Rrna Gene ◽  
Bacterial Cells ◽  
Intergenic Spacer Region ◽  
Causative Microorganism ◽  
The Impact

<p><strong>Introduction</strong></p> <p>In Infective Endocarditis (IE), early diagnosis of the causative microorganism is crucial for correct antibiotic therapy, which improves the patients’ outcome.</p> <p><strong>Objectives</strong></p> <p>We studies the impact of biofilm formation in IE samples.</p> <p><strong>Materials & methods</strong></p> <p>We used Fluorescence in situ Hybridization (FISH) combined with 16S rRNA-gene PCR and sequencing to visualize and identify the infectious agents in native as well as prosthetic valves and to study any biofilm formation. The signal intensity of the fluorescence-labelled FISH probes correlates to a high ribosome content of the bacteria indicating metabolic activity at the time point of surgery. We developed a spacer FISH assay for the detection of the 16S-23S intergenic spacer region that is only present in actively transcribing cells to detect the activity of bacterial cells more precisely on a single cell level.</p> <p><strong>Results</strong></p> <p>FISH visualized bacteria in the heart valves ranging from single cells to highly organized biofilms. Interestingly, we found FISH positive bacteria in culture negative samples and samples from patients under antibiotic therapy. Using the spacer FISH, we visualized positive microbial cells in heart valves of patients under adequate therapy. Preliminary data point to a correlation between the biofilm state and treatment inefficiency.</p> <p><strong>Conclusion</strong></p> <p>FISH/PCR not only allows timely identification of the pathogens in IE, but also biofilm-staging and visualization of the effect of antimicrobial therapy at time of surgery. The technique provides crucial information for successful targeted antibiotic therapy, and it might guide therapeutical decisions in relation to biofilm state in the future.</p>

scholarly journals Repurposing Toremifene for Treatment of Oral Bacterial Infections

2016 ◽  
Vol 61 (3) ◽  
Author(s):  
Evelien Gerits ◽  
Valerie Defraine ◽  
Katleen Vandamme ◽  
Kaat De Cremer ◽  
Katrijn De Brucker ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Bacterial Infections ◽  
Antibacterial Agents ◽  
Anticancer Agent ◽  
Treatment Strategies ◽  
Drug Repurposing ◽  
Oral Bacteria ◽  
Content Type ◽  
New Treatment ◽  
Time Kill

ABSTRACT The spread of antibiotic resistance and the challenges associated with antiseptics such as chlorhexidine have necessitated a search for new antibacterial agents against oral bacterial pathogens. As a result of failing traditional approaches, drug repurposing has emerged as a novel paradigm to find new antibacterial agents. In this study, we examined the effects of the FDA-approved anticancer agent toremifene against the oral bacteria Porphyromonas gingivalis and Streptococcus mutans. We found that the drug was able to inhibit the growth of both pathogens, as well as prevent biofilm formation, at concentrations ranging from 12.5 to 25 μM. Moreover, toremifene was shown to eradicate preformed biofilms at concentrations ranging from 25 to 50 μM. In addition, we found that toremifene prevents P. gingivalis and S. mutans biofilm formation on titanium surfaces. A time-kill study indicated that toremifene is bactericidal against S. mutans. Macromolecular synthesis assays revealed that treatment with toremifene does not cause preferential inhibition of DNA, RNA, or protein synthesis pathways, indicating membrane-damaging activity. Biophysical studies using fluorescent probes and fluorescence microscopy further confirmed the membrane-damaging mode of action. Taken together, our results suggest that the anticancer agent toremifene is a suitable candidate for further investigation for the development of new treatment strategies for oral bacterial infections.

scholarly journals Plasmapheresis and corticosteroids in infective endocarditis-related crescentic glomerulonephritis

2019 ◽  
Vol 12 (3) ◽  
pp. e227672 ◽  
Author(s):  
Kunal Malhotra ◽  
Preethi Yerram
Keyword(s):  
Infective Endocarditis ◽  
Antibiotic Therapy ◽  
Crescentic Glomerulonephritis ◽  
Septal Defect ◽  
High Dose ◽  
Ventricular Septal Defect Closure ◽  
Night Sweats ◽  
Baseline Creatinine ◽  
Subsequent Improvement

Infective endocarditis (IE)-related glomerulonephritis (GN) typically resolves with the treatment of IE. A 59-year-old woman with a baseline creatinine of 0.7 mg/dL presented with rash on her legs, night sweats and weight loss for 3 weeks. Further evaluation revealed IE. Her blood cultures grew gamma-haemolytic streptococcus, which subsequently cleared on appropriate antibiotic therapy. Her creatinine, however, progressively worsened requiring haemodialysis. Kidney biopsy showed immune complex-mediated necrotising and crescentic GN. She was started on plasmapheresis (PE) and high-dose steroids with rapid taper, with subsequent improvement in her creatinine to 0.8 mg/dL. She subsequently had aortic valve replacement and ventricular septal defect closure. She did not improve as expected with antibiotic therapy but turned around dramatically with steroids and PE. Our case supports the possible beneficial role of PE and steroids in IE-related crescentic GN that worsens despite appropriate antibiotic therapy, although the risks of immunosuppression and aggravating endocarditis need to be considered.

scholarly journals Prevention of the infective endocarditis during the dental procedures

2005 ◽  
Vol 52 (3) ◽  
pp. 152-154
Author(s):  
Tatjana Puskar ◽  
S. Puskar ◽  
Z. Nikolic
Keyword(s):  
Infective Endocarditis ◽  
Heart Valves ◽  
Wide Spectrum ◽  
Prosthetic Heart Valves ◽  
Heart Defect ◽  
Dental Procedures ◽  
Dental Intervention ◽  
Infective Disease ◽  
Risk Patients ◽  
Circulation Of The Blood

Endocarditis is endovascular infective disease of intracardiac structures, which are in contact with blood. The most common cause is Staphylococcus aureus and Streptococcus viridans, which inhabit oral cavity. During dental intervention, which includes gingival trauma (risky dental intervention) microorganisms that cause infective endocarditis could penetrate into circulation of the blood. The group of high risk patients consists of patients which have already had infective endocarditis, patients with prosthetic heart valves or other foreign endovascular bodies, patients with congenital heart defect, patients with acquired heart defect, prolapse of mitral valve with registered mitral regurgitation and hyphertrophic cardiomiopathy. Those groups of patients should have prevention from infective endocarditis before any risky dental intervention with bactericidal dosage of wide spectrum antibiotics at least an hour before the procedure. .

scholarly journals Clinical Options in Relapsed or Refractory Hodgkin Lymphoma: An Updated Review

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Roberta Fedele ◽  
Massimo Martino ◽  
Anna Grazia Recchia ◽  
Giuseppe Irrera ◽  
Massimo Gentile ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Treatment Strategies ◽  
Clinical Results ◽  
High Dose Chemotherapy ◽  
Immune Checkpoints ◽  
High Dose ◽  
Drug Conjugates ◽  
New Treatment ◽  
Established Role

Hodgkin lymphoma (HL) is a potentially curable lymphoma, and modern therapy is expected to successfully cure more than 80% of the patients. Second-line salvage high-dose chemotherapy and autologous stem cell transplantation (auto-SCT) have an established role in the management of refractory and relapsed HL, leading to long-lasting responses in approximately 50% of relapsed patients and a minority of refractory patients. Patients progressing after intensive treatments, such as auto-SCT, have a very poor outcome. Allogeneic SCT represents the only strategy with a curative potential for these patients; however, its role is controversial. Based on recent knowledge of HL pathology, biology, and immunology, antibody-drug conjugates targeting CD30, small molecule inhibitors of cell signaling, and antibodies that inhibit immune checkpoints are currently explored. This review will discuss the clinical results regarding auto-SCT and allo-SCT as well as the current role of emerging new treatment strategies.

Advances in the Diagnosis and Treatment of Infective Endocarditis

2017 ◽  
pp. 175-193
Author(s):  
R. Brigg Turner ◽  
Jacqueline Schwartz
Keyword(s):  
Infectious Disease ◽  
Infective Endocarditis ◽  
Adverse Events ◽  
Physical Examination ◽  
Antibiotic Therapy ◽  
Bacterial Infection ◽  
Heart Valves ◽  
Drug Resistant ◽  
Mortality And Morbidity ◽  
Causative Microorganism

Infective endocarditis is a relatively uncommon infectious disease that leads to substantial mortality and morbidity. This disease primarily involves bacterial infection of the heart valves. Diagnosis is contingent upon excellent physical examination and radiological and microbiological evidence. While failure to identify the causative microorganism does not preclude the diagnosis of infective endocarditis, management is more difficult. Recent advances have improved the etiological identification and allowed for shorter time to optimal antibiotic therapy. Advances in treatment have focused on therapies to combat drug-resistant microorganisms as well as mitigate adverse events. While new therapies are available, there exists a paucity of clinical evidence and further studies are required.

Current concepts of the interventional treatment of proximal supraaortic vessel stenosis

VASA ◽  
2012 ◽  
Vol 41 (5) ◽  
pp. 313-318 ◽  
Author(s):  
Ernemann ◽  
Bender ◽  
Melms ◽  
Brechtel ◽  
Kobba ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Carotid Bifurcation ◽  
Current Treatment ◽  
Long Term Results ◽  
Clinical Indication ◽  
Interventional Treatment ◽  
Special Focus ◽  
Brachiocephalic Artery ◽  
Treatment Concepts ◽  
Angioplasty And Stenting

Interventional therapies using angioplasty and stenting of symptomatic stenosis of the proximal supraaortic vessels have evolved as safe and effective treatment strategies. The aim of this paper is to summarize the current treatment concepts for stenosis in the subclavian and brachiocephalic artery with regard to clinical indication, interventional technique including selection of the appropriate vascular approach and type of stent, angiographic and clinical short-term and long-term results and follow-up. The role of hybrid interventions for tandem stenoses of the carotid bifurcation and brachiocephalic artery is analysed. A systematic review of data for angioplasty and stenting of symptomatic extracranial vertebral artery stenosis is discussed with a special focus on restenosis rate.

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