Association of persistent positive blood cultures and infective endocarditis: A cohort study among patients with suspected infective endocarditis.

OBJECTIVES: To ascertain whether infective endocarditis (IE) was associated with persistent bacteraemia/candidaemia among patients with suspected IE. METHODS: This study included bacteraemic/candidaemic adult patients with echocardiography and follow-up blood cultures. Persistent bacteraemia/candidaemia was defined as continued positive blood cultures with the same microorganism for 48 h or more after antibiotic treatment initiation. Each case was classified for IE by the Endocarditis Team. RESULTS: Among 1962 episodes of suspected IE, IE (605; 31%) was the most prevalent infection type. Persistent bacteraemia/candidaemia was observed in 426 (22%) episodes. Persistent bacteraemia was more common among episodes with Staphylococcus aureus bacteraemia compared to episodes with positive blood cultures for other pathogens (32%, 298/933 vs 12%, 128/1029; P < 0.001). Multivariable analysis demonstrated that cardiac predisposing factors (aOR 1.84, 95% CI 1.31-2.60), community or non-nosocomial healthcare-associated (2.85, 2.10-3.88), bacteraemia by high-risk bacteria, such as S. aureus, streptococci, enterococci or HACEK (1.84, 1.31-2.60), two or more positive sets of index blood cultures (6.99, 4.60-10.63), persistent bacteraemia/candidaemia for 48 h from antimicrobial treatment initiation (1.43, 1.05-1.93), embolic events within 48h from antimicrobial treatment initiation (12.81, 9.43-17.41), and immunological phenomena (3.87, 1.09-1.78) were associated with infective endocarditis. CONCLUSIONS: IE was associated with persistent bacteraemia/candidaemia, along with other commonly associated factors.

Behçet's syndrome masquerading as infective endocarditis: A diagnostic conundrum and therapeutic challenge.

This case report presents a 20-year-old male patient initially diagnosed with infective endocarditis, later correctly identified as Behçet's syndrome. The patient's complex clinical presentation, including chest pain, aortic dilation, severe aortic regurgitation, and aortic root abscess, posed significant diagnostic and therapeutic challenges. Despite initial misdiagnosis and treatment difficulties, the patient's condition significantly improved with appropriate immunosuppressive therapy, underscoring the potential for successful management of this complex condition. This case serves as a valuable reminder of the diagnostic challenges posed by Behçet's syndrome and the importance of considering this condition in patients presenting with symptoms suggestive of infective endocarditis.

Outpatient parenteral antibiotic treatment for infective endocarditis: A retrospective observational evaluation.

BACKGROUND: Infective endocarditis (IE) requires long courses of intravenous (IV) antibiotics. Outpatient parenteral antibiotic therapy (OPAT) saves resources, improves the patient experience and allows care in their preferred place; however, questions remain about safety when treating IE patients. This study evaluates OPAT management of IE patients in our region between 2006 and 2019. METHODS: This is a retrospective observational evaluation and description of outcomes and adherence to suitability criteria, according to British Society for Antimicrobial Chemotherapy (BSAC) guidelines. RESULTS: We identified five models of OPAT delivery. The number of patients treated expanded significantly over time. Of 101 patients, six (6%) suffered poor outcomes, but each patient had contributing factors outside of the primary infection. Median OPAT duration was 12 days and 1,489 hospital bed days were saved. CONCLUSIONS: In a setting where there was good adherence to BSAC criteria, treating IE patients using OPAT services was safe. Complications observed were likely independent of treatment location. Significant bed days were saved.

Comparative effectiveness of empirical antibiotic treatments in methicillin-susceptible Staphylococcus aureus infective endocarditis: A post hoc analysis of a prospective French cohort study.

OBJECTIVES: The empirical treatment of infective endocarditis is still debated. The aim of this study was to compare the impact of empirical treatment with antistaphylococcal penicillin (ASP) or cefazolin vs. other treatments in methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis. METHODS: A post hoc analysis of a prospective cohort study of patients hospitalized in a French reference centre with MSSA endocarditis was conducted between 2013 and 2022. The primary outcome was the duration of bacteraemia under treatment. RESULTS: Of the 208 patients included, 101 patients (48.6%) were classified in the reference group (ASP or cefazolin) and 107 (52.4%) in the non-reference group. Empirical treatment with ASP/cefazolin was associated with a shorter duration of bacteraemia compared to other treatments (3.6 d vs. 4.6 d, P = 0.01). This difference was not corrected by the addition of an aminoglycoside (3.6 d vs. 4.7 d, P < 0.01). In multivariate analysis, empirical treatment with ASP/cefazolin was associated with a duration of bacteraemia ≤72 h (P = 0.02), whereas endocarditis on native valves (P = 0.01), and intracardiac abscess were associated with longer duration of bacteraemia (P = 0.01). CONCLUSIONS: Empirical treatment of endocarditis with ASP or Cefazolin is more effective than other treatments in MSSA endocarditis, even when the other treatments are combined with aminoglycosides.

Antimicrobial susceptibility of Viridians Group of Streptococci isolated from infective endocarditis patients from 2018 to 2023.

INTRODUCTION: Viridans Group of Streptococci (VGS) are heterogeneous alpha hemolytic Streptococci that form commensal flora in the oral cavity, upper respiratory tract, gastrointestinal tract and female genital tract and are potential pathogens that can cause serious infections like infective endocarditis and bacteremia. Penicillin or Ceftriaxone is the recommended first line agent for definitive therapy of VGS endocarditis. Alteration in penicillin binding proteins can decrease the susceptibility of VGS to penicillin and other beta-lactam agents and complicate antimicrobial therapy for serious VGS infections like Infective endocarditis. The aim of our study was to determine the antimicrobial susceptibility pattern of viridians group Streptococci isolated from blood samples of infective endocarditis patients from April 2018 to September 2023 against betalactam and other agents. MATERIAL AND METHODS: Three sets of blood cultures with 8-10 ml per bottle were collected from suspected infective endocarditis and incubated in automated blood culture system (BACTEC from BD diagnostics). The broth from positive bottles was streaked on Blood agar, Chocolate agar and MacConkey agar plates and incubated at 37°C. Alpha hemolytic Streptococci that grew after 24-48 h were further identified and antimicrobial susceptibility determined by Vitek 2 system. RESULTS: A total of 100 VGS was isolated from blood samples of Infective endocarditis patients. The species most commonly isolated in our study was S. sanguinis (25%) and S.mitis/oralis group (23%) followed by Non speciated Viridans Streptococci (17%). The lowest penicillin susceptibility ie. PEN MIC <0.12 µg/ml of 40% was observed in S. alactolyticus group, followed by S. mitis (52%) and S. gallolyticus (56%). S. mitis/oralis group showed the lowest susceptibilities to betalactam antibiotics among all speciated and non speciated VGS. CONCLUSION: Infective endocarditis carries a very high mortality and morbidity and the emergence of resistance to betalactam agents like penicillin will only narrow available therapeutic options and further challenge the treatment.

Getting to the heart of the matter-are two agents really better than one for the treatment of staphylococcal infective endocarditis?

The recently published European Society of Cardiology guidelines for infective endocarditis management recommends daptomycin combination therapy for the treatment of staphylococcal endocarditis in severe penicillin allergy, rather than daptomycin monotherapy. We discuss the evidence base behind this recommendation, highlighting concerns regarding the lack of robust clinical studies, increased cost and logistical considerations, and adverse effects of combination therapy. Although further studies are required to elucidate the role of combination vs monotherapy in these patients, we propose a pragmatic management approach to reduce the risk of adverse antimicrobial side effects and limit costs, while aiming to maintain treatment efficacy.

Suppressive antibiotic therapy for infectious endocarditis.

OBJECTIVES: Suppressive antibiotic therapy (SAT) is a long-term antibiotic strategy at times applied when an indicated surgical management of infective endocarditis (IE) is not possible. Our aim was to describe the characteristics and outcomes of patients having received SAT for IE. METHODS: We conducted a retrospective, observational study at Strasbourg University Hospital, France between January 2020 and May 2023. We reviewed all medical files taken into consideration at weekly meetings of the local Multidisciplinary Endocarditis Team (MET) during the study period. We included patients having received SAT following the MET evaluation. The primary endpoint was all-cause mortality at most recent follow-up. Secondary endpoints included all-cause mortality at 3 and 6 months, infection relapse, and tolerance issues attributed to SAT. RESULTS: The MET considered 251 patients during the study time, among whom 22 (9 %) had received SAT. Mean age was 77.2 ± 12.3 years. Patients were highly comorbid with a mean Charlson index score of 6.6 ± 2.5. Main indication for SAT was surgery indicated but not performed or an infected device not removed (20/22). Fourteen patients had prosthetic valve IE, including 9 TAVIs. Six patients had IE affecting cardiac implantable electronic devices. Staphylococcus aureus and enterococci were the main bacteria involved (6/22 each). Median follow-up time was 249 days (IQR 95-457 days). Mortality at most recent follow-up was 23 % (5/22). Three patients (14 %) presented tolerance issues attributed to SAT, and two patients suffered late infectious relapse. CONCLUSION: Mortality at most recent follow-up was low and tolerance issues were rare for patients under SAT, which might be a palliative approach to consider when optimal surgery or device removal is not possible.

C-terminal deletion of RelA protein is suggested as a possible cause of infective endocarditis recurrence with Enterococcus faecium.

Infective endocarditis (IE) caused by Enterococcus spp. represents the third most common cause of IE, with high rates of relapse compared with other bacteria. Interestingly, late relapses (>6 months) have only been described in Enterococcus faecalis, but here we describe the first reported IE relapse with Enterococcus faecium more than a year (17 months) after the initial endocarditis episode. Firstly, by multi locus sequence typing (MLST), we demonstrated that both isolates (EF646 and EF641) belong to the same sequence type (ST117). Considering that EF641 was able to overcome starvation and antibiotic treatment conditions surviving for a long period of time, we performed bioinformatic analysis in identifying potential genes involved in virulence and stringent response. Our results showed a 13-nucleotide duplication (positions 1638-1650) in the gene relA, resulting in a premature stop codon, with a loss of 167 amino acids from the C-terminal domains of the RelA enzyme. RelA mediates the stringent response in bacteria, modulating levels of the alarmone guanosine tetraphosphate (ppGpp). The relA mutant (EF641) was associated with lower growth capacity, the presence of small colony variants, and higher capacity to produce biofilms (compared with the strain EF646), but without differences in antimicrobial susceptibility patterns according to standard procedures during planktonic growth. Instead, EF641 demonstrated tolerance to high doses of teicoplanin when growing in a biofilm. We conclude that all these events would be closely related to the long-term survival of the E. faecium and the late relapse of the IE. These data represent the first clinical evidence of mutations in the stringent response (relA gene) related with E. faecium IE relapse.

Differential in vitro susceptibility to ampicillin/ceftriaxone combination therapy among Enterococcus faecalis infective endocarditis clinical isolates.

OBJECTIVES: To investigate the genomic diversity and ß-lactam susceptibilities of Enterococcus faecalis collected from patients with infective endocarditis (IE). METHODS: We collected 60 contemporary E. faecalis isolates from definite or probable IE cases identified between 2018 and 2021 at the University of Pittsburgh Medical Center. We used whole-genome sequencing to study bacterial genomic diversity and employed antibiotic checkerboard assays and a one-compartment pharmacokinetic-pharmacodynamic (PK/PD) model to investigate bacterial susceptibility to ampicillin and ceftriaxone both alone and in combination. RESULTS: Genetically diverse E. faecalis were collected, however, isolates belonging to two STs, ST6 and ST179, were collected from 21/60 (35%) IE patients. All ST6 isolates encoded a previously described mutation upstream of penicillin-binding protein 4 (pbp4) that is associated with pbp4 overexpression. ST6 isolates had higher ceftriaxone MICs and higher fractional inhibitory concentration index values for ampicillin and ceftriaxone (AC) compared to other isolates, suggesting diminished in vitro AC synergy against this lineage. Introduction of the pbp4 upstream mutation found among ST6 isolates caused increased ceftriaxone resistance in a laboratory E. faecalis isolate. PK/PD testing showed that a representative ST6 isolate exhibited attenuated efficacy of AC combination therapy at humanized antibiotic exposures. CONCLUSIONS: We find evidence for diminished in vitro AC activity among a subset of E. faecalis IE isolates with increased pbp4 expression. These findings suggest that alternate antibiotic combinations against diverse contemporary E. faecalis IE isolates should be evaluated.

Talaromyces marneffei endocarditis initially detected by Next Generation Sequencing: A case report.

BACKGROUND: Talaromyces marneffei (T. marneffei) is a thermal dimorphic fungus, which can cause lung or blood stream infection in patients, often life-threatening. However, endocarditis caused by T. marneffei has not been reported. For elderly patients with implanted cardiac devices or artificial valves, the prevention and treatment of infective endocarditis should not be ignored. METHODS: This is a descriptive study of a T. marneffei endocarditis by joint detection of cardiac ultrasound examination, peripheral blood DNA metagenomics Next Generation Sequencing (mNGS), and in vitro culture. RESULTS: We describe an 80-year-old female patient with an unusual infection of T. marneffei endocarditis. After intravenous drip of 0.2 g voriconazole twice a day for antifungal treatment, the patient showed no signs of improvement and their family refused further treatment. CONCLUSION: Infective endocarditis is becoming more and more common in the elderly due to the widely use of invasive surgical procedures and implantation of intracardiac devices. The diagnosis and treatment of T. marneffei endocarditis is challenging because of its rarity. Here, we discussed a case of T. marneffei endocarditis, and emphasized the role of mNGS in early diagnosis, which is of great significance for treatment and survival rate of patients.

A Novel Potential Biomarker for Predicting the Development of Septic Embolism in Patients with Infective Endocarditis: Systemic Coagulation Inflammation Index.

OBJECTIVE: Early diagnosis of septic emboli is crucial to prevent the associated morbidity and mortality. This study aimed to examine the relationship between the systemic coagulation inflammation index (SCII) and septic embolism in patients with infective endocarditis (IE). METHODS: We retrospectively analyzed the data of 167 IE patients treated at our tertiary care hospital between January 2007 and January 2023. We collected information on symptoms, comorbidities, predisposing valve diseases, prosthetic valves, devices, history of injectable drug use, blood culture results, echocardiographic findings, and complications. The SCII index was calculated using the formula: [platelet count (PLT) × fibrinogen level (g/L) / white blood cell count (WBC)]. RESULTS: The mean age of the patients was 61 years, with rheumatic valve disease being the most common predisposing factor. The most common etiologic microorganism was Staphylococcus species. Septic embolism developed in 25.7% of the patients, with the cerebral system being the most commonly affected (46.5%). The SCII was identified as an independent marker for the development of septic embolism. Receiver operating characteristic (ROC) curve analysis confirmed that an optimal SCII value of 59.8 predicted septic emboli with a sensitivity of 65.1% and a specificity of 59.6% (area under the ROC curve: 0.649 [95% confidence interval (CI): 0.556 - 0.743], P = 0.004). CONCLUSION: This study demonstrates that high SCII levels are an independent predictor for the development of septic embolism in patients with IE.

Delayed formation and rupture of intracranial aneurysm following Abiotrophia defectiva endocarditis.

Abiotrophia defectiva is a type of Streptococci and is a rare cause of infectious endocarditis. The progression and outcomes of infectious intracranial aneurysms (IIAs) associated with this species are unknown due to a limited number of reported cases. A woman in her 20s with a sudden headache had a subarachnoid haemorrhage on a head CT scan. Cerebral angiography showed an aneurysm on the right middle cerebral artery. She was diagnosed with infectious endocarditis caused by A. defectiva and underwent parent artery occlusion. Despite initiating targeted antibiotic therapy, a new IIA developed and ruptured 14 days postadmission. A second parent artery occlusion was performed on the new IIA. Following 6 weeks of continued antibiotic therapy, she underwent mitral valve repair and was discharged with no neurological symptoms. Endocarditis caused by A. defectiva can lead to the delayed formation of an IIA. Endovascular treatment was effective for repeated ruptured IIAs.

Burkholderia cepacia: A Rare Source of Endocarditis.

A 37-year-old male with a past medical history of previous mitral valve replacement due to bacterial endocarditis and intravenous (IV) drug use was found to have Burkholderia cepacia bacteremia. Transesophageal echocardiogram revealed large mitral and tricuspid valve vegetations. Medical management was initially attempted but his bacteremia persisted, and he required urgent prosthetic mitral valve replacement and native tricuspid valve replacement. Prosthetic valve endocarditis has been associated with surgery in 48.9% of patients and a mortality of 22.8%. In patients with prosthetic valve endocarditis due to B. cepacia, valve replacement occurred in approximately 61.5% of patients and mortality is estimated to be 33.3%. To our knowledge, this is one of only a few prosthetic valve endocarditis cases caused solely by B. cepacia and our case is the first to affect multiple valves including prosthetic and native valves.